RU2059620C1 - Arylpyrrol derivatives, method of their synthesis, intermediate compounds and a method of struggle against insects, nematodes and ticks - Google Patents

Abstract

FIELD: organic chemistry. SUBSTANCE: products: derivatives of arylpyrrol of the formula

where X - Cl, Br, J or CF₃; Y - Cl, Br, J, CF₃ or CN; W - CN or NO₂; A - hydrogen, nonsubstituted C₁-C₄-alkyl or that substituted with halogen, hydroxy-group, C₁-C₄-alkoxy, C₁-C₄-alkylthio- or phenyl-group, phenoxy - or C₁-C₂-alkoxyphenyl-group; C₁-C₄-carbalkoxymethyl; nonsubstituted C₃-C₄-alkenyl or that substituted with a single halogen; cyano-group; nonsubstituted C₃-C₄-alkynyl or that substituted with a single halogen; di-(C₁-C₄)-alkylaminocarbonyl; L - hydrogen, fluorine, chlorine or bromine; M and R - every independently is hydrogen, C₁-C₃-alkyl, C₁-C₃-alkoxy, C₁-C₃-alkylsulfonyl-groups, cyano, fluorine, chlorine, bromine, iodine, nitro, CF₃, groups R₁CF₂Z or R₂CO where Z - oxygen, R₁ - fluorine or CHF₂; R₂ - C₁-C₃-alkyl. Reagent 1: benzoylacetonitrile or α-nitroacetophenone of the formula

where L, M, R and W as indicated above. Reagent 2: 2,2-di-((C₁-C₄)-alkoxy)-ethylamine. Synthesized compounds were used for struggle against insects, nematodes and ticks. ??? EFFECT: improved method of synthesis. 5 cl

Description

 The invention is directed to new arylpyrrole compounds, which are highly effective insecticidal, acaricidal and nematicidal agents. In addition, this invention provides for the protection of crops during cultivation and harvesting against the harmful effects of these pests.

 The present invention is also directed to methods for producing arylpyrrole compounds.

где X хлор, бром, йод или CF₃;
Y хлор, бром, йод, CF₃ или CN;
W-CN или NO₂;
А водород; С₁-С₄-алкил, незамещенный или замещенный галогеном, гидрокси-, С-С₄-алкокси-, С₁-С₄-алкилтио или фенильной группой, фенокси-, или С₁-С₂-алкоксифенильной группой; С₁-С₄-карбалкоксиметил; С₃-С₄-алкенил, незамещенный или замещенный одним галогеном; цианогруппа; С₃-С₄-алкинил, незамещенный или замещенный одним галогеном; ди(С₁-С₄)алкиламинокарбонил; L водород, фтор, хлор или бром; М и R каждый независимо представляет собой водород, С₁-С₃-алкил. С₁-С₃ алкокси-, С₁-С₃ алкилсульфонил-группы, циано, фтор, хлор, бром, йод, нитро, CF₃, группы R₁CF₂Z- или R₂CO-, где Z кислород, R₁ фтор или СНF₂, R₂ C₁-C₃-алкил, и когда группы М и R находятся в соседних положениях, они совместно с атомами углерода, с которыми связаны, образуют кольцо, где группа МR является -СН=СН-СН=СН-.New derivatives of arylpyrrole have the general formula:
_X _

where X is chlorine, bromine, iodine or CF ₃ ;
Y is chloro, bromo, iodo, CF ₃ or CN;
W-CN or NO ₂ ;
And hydrogen; C ₁ -C ₄ alkyl unsubstituted or substituted by halogen, hydroxy, C ₄ -C ₄ alkoxy, C ₁ -C ₄ alkylthio or phenyl group, phenoxy or C ₁ -C ₂ alkoxyphenyl group; C ₁ -C ₄ carbalkoxymethyl; C ₃ -C ₄ alkenyl unsubstituted or substituted with one halogen; cyano group; C ₃ -C ₄ alkynyl unsubstituted or substituted with one halogen; di (C ₁ -C ₄ ) alkylaminocarbonyl; L is hydrogen, fluoro, chloro or bromo; M and R each independently represents hydrogen, C ₁ -C ₃ alkyl. C ₁ -C ₃ alkoxy, C ₁ -C ₃ alkylsulfonyl groups, cyano, fluoro, chloro, bromo, iodo, nitro, CF ₃ , groups R ₁ CF ₂ Z- or R ₂ CO-, where Z is oxygen, R ₁ fluorine or CHF ₂ , R ₂ C ₁ -C ₃ -alkyl, and when the groups M and R are in adjacent positions, they together with the carbon atoms to which they are attached form a ring, where the group MR is —CH = CH — CH = CH-.

где L, M, R и W имеют вышеуказанные значения.In addition, the invention relates to new intermediates for the preparation of arylpyrrole derivatives with derivatives of β-nitro and β-cyanostyrene, in particular: α- (2,2-di (C _1-4 alkoxy) ethylamino) - β-cyanostyrene and α- (2 , 2-di (C _1-4 alkoxy) ethylamino) - β-nitrostyrene of the general formula

where L, M, R and W have the above meanings.

-CH₂W где L, M, R и W имеют вышеуказанные значения, подвергают взаимодействию с 2,2-ди(С_1-4алкокси)этиламином и полученные при этом соответственно α-(2,2-ди (С₁-С₄алкокси)этиламино)- β-цианостирол или α-(2,2-ди(С₁-С₄алкокси)этиламино)- β-нитростирол обрабатывают минеральной или органической кислотой.These intermediates are obtained in one of the steps of the process for preparing arylpyrrole derivatives of the general formula 1, which consists in the fact that benzoylacetonitrile or α-nitroacetophenone of the general formula

-CH ₂ W where L, M, R and W have the above meanings, are reacted with 2,2-di (C _1-4 alkoxy) ethylamine and the resulting α- (2,2-di (C ₁ -C ₄ alkoxy) ethylamino) - β-cyanostyrene or α- (2,2-di (C ₁ -C ₄ alkoxy) ethylamino) - β-nitrostyrene is treated with a mineral or organic acid.

 Examples of a number of benzoylacetonitriles are given below in table 1.

 In addition, the invention relates to a method for controlling insects, nematodes and ticks by treating them with an arylpyrrole derivative, which consists in using a compound of general formula 1 (where the radical values are given above) in an effective amount as an arylpyrrole.

 The arylpyrroles of the present invention are effective in controlling insects, parasitic mites and nematodes. These compounds are also effective in protecting crops grown or harvested from the attack of the aforementioned pests.

 In practical conditions, they are usually effective in the approximate range of 10 to 10,000 ppm, and preferably 100 to about 5,000 ppm arylpyrrole of formula 1, covering all isomers of arylpyrrole dispersed in water or another cheap liquid carrier when applied to planting material cultivated crops or on the soil where the mentioned planting material is grown to protect it from attack by pests.

 When applied to foliage of planting material and / or to the soil or water where such material is grown, the applied amount should be sufficient to ensure the amount of active ingredient in the range from 0.125 to 4.0 kg / ha. Obviously, it is possible to use higher ratios when applying arylpyrroles of formula 1 to protect planting material from attack by insect pests of nematodes and parasitic mites. However, higher application ratios are usually not necessary to avoid overhead. Although the arylpyrroles of the present invention are effective in themselves for controlling pests, they can be used in conjunction with other biologically active chemical products, including other insecticides, nematicides and acaricides.

 Conveniently, the arylpyrroles mentioned above are included in the formulation. These include dry compact granules, flowable compositions, wettable powders, emulsifiable concentrates, dusts, dust concentrates, microemulsions, etc. capable of applying to soil, water and / or foliage and provide the necessary protection for the plant. Such formulations include the compounds of the invention in admixture with inert, agriculturally acceptable solid or liquid diluents. Liquid formulations of the compounds of the invention to be sprayed should contain approximately 0.001 to 0.1 wt. active arylpyrrole.

 In conditions of use in row plantings, volumes of 200-500 l / ha are used, which usually corresponds to a dose of 0.02-0.05 kg / ha at a dose of 100 ppm and 0.2-0.5 kg / ha at a dose of 1000 ppm

 Similarly, when used in garden plantings, volumes of 1,250-4,000 l / ha are used, which corresponds to a dose of 0.125-0.4 kg / ha at a dose of 100 ppm and 1.25-4.0 kg / ha at a dose of 1000 ppm . (see tab. 2).

 PRI me R 1. 2-phenylpyrrole-3-carbonitrile.

The following procedure is similar to the method given in OX 43, 4273-6 (1978). A magnetically stirred mixture of 30.00 g of N-formyl-phenylglycine is heated at 90 ° ^C for 1.5 hours. The clear yellow reaction solution was concentrated in vacuo to give 42.5 g of an oily brownish orange semi-solid material. Part of the material, purified by chromatography on silica gel, showed by the proton NMR spectrum a mixture of 73% 2-phenylpyrrole-3-carbonitrile and 27% 2-phenylcyano-5-methylpyrrole. A single recrystallization from chloroform and a double recrystallization from 1,2-dichloroethane gave 1.69 off-white solid, the proton NMR of which showed the presence of 96% 2-phenyl-pyrrole-3-carbonitrile, so pl. 148-152 ^about S.

Microanalysis (M.V. 168.19):
Calculated: C 78.55; H 4.79; N 16.66%
Found: C, 78.52; H 4.73; N, 16.54.

 PRI me R 2. 4,5-dichloro-2-phenylpyrrole-3-carbonitrile and 5-chloro-2-phenylpyrrole-3-carbonitrile.

To a solution of 2.00 (11.9 mmol) of 2-phenyl-3-cyanopyrrole in 80 ml of methylene chloride, which is stirred with a magnetic stirrer and ice-cold water, 1.90 ml (3.19 g; 23.6 mmol) are added dropwise over 5 minutes sulfuryl chloride with a syringe. During the addition the temperature is maintained in the range of 5-10 ^C. Stirring at 5-10 ^{° C} continued for 90 minutes. The reaction mixture was filtered in vacuo to remove precipitated solid (1.28 g), identified as 5-chloro-2-phenylpyrrole-3-carbonitrile, so pl. 192.5-195 ^about C. The filtrate is diluted with 400 ml of ethyl acetate, washed twice with 200 ml of water, dried (sodium sulfate), treated with activated carbon, filtered and then concentrated in vacuo. Received (after stirring the residue in hexane) 0.60 g (21.3% yield) of a pinkish-purple solid. This solid was recrystallized from 5 ml of hot acetone to give 0.32 g (9% yield) of 4,5-dichloro-2-phenylpyrrole-3-carbonitrile as a brownish-orange solid, mp. 254-255 ^about S.

H-NMR (dimethyl sulfoxide): δ 7.73 (doublet, J = 6.6 Hz; 1.97 N, 2 phenyl protons at C-2.6), δ 7.52 (triplet, J = 7.3 Hz , 2.04 N, two phenyl protons at C-3.5), δ 7, 44 (triplet, J = 7.3 Hz, 1.02 N, one phenyl proton at C-5), δ 7.52 ( triplet, J = 7.3 Hz, 2.04 N, two phenyl protons at C-3.5)
H-NMR (dimethyl sulfoxide): δ 137.51 (C-2 pyrrole carbon), δ 129.15 (C-4 phenyl carbon), δ 129.04 (C-3.5 phenyl carbon), δ 128.37 ( C-1 phenyl carbons). δ 125.88 (C-2.6 phenyl carbons), δ 114.32 (or C-5 pyrrole or nitrile carbon), δ 114.14 (or C-5 pyrrole or nitrile carbon), δ 110.72 (C -4 pyrrole carbon), δ 89.78 (C-3 pyrrole carbon).

Microanalysis (M.V. 237.09): Calculated: C 55.72; H 2.55; N, 11.82; Cl 29.91% Found: C 55.78; H 2.59; N, 11.12; Cl 29.74%
PRI me R 3. p-chloro-β - ((formylmethyl) amino) cinnamon nitrile, Diethyl acetal.

 A solution stirred with a magnetic stirrer of 250.00 g (1.39 mol) of p-chlorobenzoylacetonitrile, 203 ml (185.95 g); 1.39 moles of 2,2-diethoxyethylamine and 1300 ml of dry toluene are heated under reflux for 20 hours. The water is collected in a Dean-Stark trap (23.8 ml; 95.2% of theory). A hot cloudy dark brown solution with a large amount of undissolved solids is filtered through a filter medium in the form of diatomaceous earth. After dilution in 200 ml of ethyl acetate, the solution was filtered through a 7 cm x 13.5 cm column of silica gel.

 The filtrate was concentrated in vacuo to give 354.38 g (86.4% yield of crude product) as a clear dark oil that gradually solidified. This solid was recrystallized from hot cyclohexane to give 324.26 g (79.1% yield) of a wax-like orange solid.

The NMR of this product showed the presence of 78% (Z) and 23% (E) of the isomeric mixture of p-chloro-β - ((formylmethyl) amino) cinnamic nitrile, diethyl acetal, so pl. 60-72 ^about S.

For another similarly obtained similar sample, the following analytical data were obtained:
H-NMR (chloroform), δ 7.47 (doublet, J = 8.6 Hz, 2.12 N, two aromatic protons), δ 7.37 (Doublet, J = 8.6 Hz, 2.12 N, two aromatic protons) δ 5.10 (E) and 4.86 (Z) (wide triplet; 1.25 N, one NH proton), δ 4.69 (Z) and 4.60 (E) (triplet, J = 5.1 Hz, 1.05 N, one methine proton of acetal carbon) δ 4.07 (E) and δ 4.05 (Z) (singlet; 0.83 N, enamine β proton), δ 3.71 ( E) and δ 3.68 (Z) (quartet, J = 7.1 Hz; 2.22 N, two methylene protons of one of the two ethoxy groups), δ 3.56 (Z) and 3.53 (E) ( quartet J = 7.1 Hz, 2.22 N two methylene protons in one of two ethoxy groups); δ 3.18 (triplet; J = 5.1 Hz; 1.77 N, two methylene protons in the erylene acetal group), δ 1.20 (triplet, J = 7.1 Hz; 4.90 N, six methyl protons of two ethoxy groups).

 C-NMR (chloroform), δ 161.21 (d-enamine carbon); δ 136.29 (Z) and δ 134.60 (E) (or C-1 or C-4 of the phenyl ring), δ 129.34 (Z) and 129.89 (E) (or C-2.6 or C-3.5 phenyl ring), δ 128.94 (Z) and 128.63 (E) (either C-2.6 or C-3.5 of the phenyl ring), 121.19 (Z) and 119.50 (E) (nitrile carbon), δ 99.43 (Z) and δ 100.63 (E) (β-amine carbon), δ 61.88 (Z) and δ 63.25 (E) (methylene carbon of the ethylamine group ; δ 15.26 (methyl carbons of ethoxy groups).

Microanalysis (MV 294.78): Calculated C 61.11; H 6.50; N 3.51; Cl 12.03% Found C, 61.25; H, 6.25; N, 9.34; Cl 12.35%
PRI me R 4. 2- (p-chlorophenyl) -pyrrole-3-carbonitrile.

To 108 ml of trifluoroacetic acid, stirred at ²³ ° C, was added 54.00 g (0.183 mol) of solid p-chloro-β - ((formylmethyl) amino) cinnamyl nitrile-diethylacetal for 45 minutes. Due to the exothermic reaction during this addition the temperature rises to 38 ^{° C} and 32 m while adding solid begins to precipitate. After 30 m stirring at room temperature, the reaction mixture was filtered under vacuum and the collected solid was washed first with trifluoroacetic acid, then with a mixture of ethyl acetate and hexane, and finally hexane. The yield is 16.83 g (45.4) of an off-white solid, mp. 165-166 ^about C. The sample prepared in the same way received the following analysis data:
H-NMR (acetone): δ 11.22 (very wide singlet, 0.99 N, 1 pyrrole Nn proton), δ 7.82 (doublet, J = 8.9 Hz; 2.46 n, two aromatic phenyl proton), 7.51 (doublet, J = 8.9 Hz, 2.46 Hz, two aromatic phenyl protons), δ 7.02 (triplet, J = 2.6 Hz, 1.01 N, one pyrrole proton at C-5), δ 6.58 (triplet, J = 2.6 G; 0.77 N, one pyrrole proton at C-4).

 C-NMR (acetone) δ 137.73 (pyrrole C-2). δ 134.42 (p-chlorophenyl at C-4), 129.93 (methine carbons at the C-2.6 phenyl ring), δ 128.07 (methine carbon at C-2.6 the phenyl ring). δ 121.21 (pyrrole carbon at C-5), δ 117.93 (nitrile carbon), δ 113.78 (pyrrole carbon at C-4), δ 90.86 (pyrrole carbon at C-3).

Microanalysis (MV 02.64): C, 65.19; H 3.48; N 13.83; Cl 17.50% Found C 64.18; H 3.52; N, 13.63; Cl 17.74%
Application of the above procedure or with the replacement of concentrated hydrochloric acid with trifluoroacetic acid gave the following compounds (see table. 3).

 The structure of the products obtained for all of the following examples was confirmed by IR, NMR and elemental analysis.

 PRI me R 5. 4,5-dichloro-2- (p-chlorophenyl) pyrrole-3-carbonitrile.

To a mechanically stirred solution of 16.83 (81.3 mmol) of 2- (p-chlorophenyl) pyrrole-3-carbonitrile in 450 ml of glacial acetic acid at 36 ^{° C} was added dropwise 14.7 mL (24.70 g, 183.0 mmol) of sulfuryl chloride over 18 m. The addition involves raising the temperature to 39 ^{° C} due to weak exothermic reactions. After an additional 16 m, the reaction mixture was filtered in vacuo. The collected solids are washed first with acetic acid, then with water. This solid after recrystallization from hot ethyl acetate has a melting point of 259-261 ^about S.

 PRI me R 6. (4,5-dibromo-2- (α α α-trifluoro-n-tolyl) -pyrrole-3-carbonitrile.

To a stirred mixture of 0.8 g of 2- (α α α-trifluoro-p-tolyl) pyrrole-3-carbonitrile in 70 ml of chloroform was added 2 ml of bromine. After stirring overnight, a white solid is collected from the mixture, collected by filtration. Thin layer chromatography (1: 1 ethyl acetate-hexane) showed the presence of a single component. Mp more than 230 ^about C.

Analysis: for C ₁₂ H ₅ Br ₂ F ₃ N ₂ Calculated C 36.55; H 1.27; N, 7.11; Br 40.61% Found C 36.40; H 1.08; N, 6.99; Br 40.55%
Following the procedures of Examples 5 and 6, however, by replacing properly substituted phenyl-pyrrole-3-carbonitrile with 2- (α α α-trifluoro-p-tolyl) -pyrrole-3-carbonitrile, the following compounds are obtained (see table 4 and 5).

 PRI me R 7. 3-nitro-2-phenylpyrrole.

Alpha nitro acetophenone (5.7 g; 0.0345 mol) in 100 ml of toluene is added to 4.6 g (0.0345 mol) of aminoacetaldehyde diethyl acetate. The reagents are transferred to a 250 ml round bottom flask equipped with a Dean-Stark trap. The trap is filled with 4A molecular sieves and the mixture is refluxed for 18 hours. Removal of toluene in vacuo gives 8.36 g of α- (2,2-diethoxyethyleneamine) -β-nitrostyrene in the form of a brown oil. To this oil add 50 ml conc. hydrochloric acid. As the flask rotates in a circular motion, the oil passes into a yellow suspension. After 10 minutes, the solid was filtered off to give 2.48 g of a yellow solid. Recrystallization from ether (ethyl acetate) hexane gives the product in the form of 2 fractions:
2.08 g. 190-192 ^about C (31%).

Max: (1485 cm ^-1 (NO ₂ ), H-NMR (deuterated chloroform / dimethyl sulfoxide) 6.73 (m, 2H); 7.46 (m, 5H).

 PRI me R 8. 2,3-dichloro-4-nitro-5-phenylpyrrole.

 A mixture of 3-nitro-2-phenylpyrrole (1.56 g; 0.0083 mol) with 60 ml of dioxane is cooled in an ice bath as 25.9 g (0.0182 mol) of commercial sodium hypochlorite are added dropwise. After 45 m stirring, the mixture was acidified with conc. hydrochloric acid. Water and diethyl ether are added. The layers were separated and the upper organic layer was washed with water, dried over anhydrous magnesium sulfate and concentrated in vacuo to give 2.21 g of a yellow solid.

Purification by chromatography using silica gel and washing from the adsorbent in increasing ratios with ethyl acetate-hexane gives 0.77 g of a yellow solid (36%) after evaporation, mp. 190-190.5 ^about C;
Analysis for C ₁₀ H ₆ N ₂ O ₂ Cl ₂
C, 46.72; H 2.35; N 10.90%
Found C, 46.96; H 2.86; N 10.02%
Following the procedures of Examples 7 and 8. above, however, using appropriately substituted α-nitroacetophenone and 2,2-di (ES ₁ -C ₄ ) alkoxy) ethylamine, substituted α-2,2-di (C ₁ -C ₄ alkoxy) ethylamine) - β-nitrostyrene, which are then converted to 3-nitro-2- (substituted) phenylpyrrole by treatment with hydrochloric acid, hydrobromic acid or CF ₃ COOH. The reaction of the thus substituted phenylpyrrole with sodium hypochlorite in dioxane gives chloro analogs; whereas the reaction of substituted phenylpyrrole with bromine in chloroform leads to analogues containing bromine (see Table 6).

 PRI me R 9. 4,5-dichloro-2- (3,4-dichlorophenyl) -1-methyl-pyrrole-3-carbonitrile.

 In a 100 ml flask, 2 g of 4,5-dichloro-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile in 60 ml of dry tetrahydrofurin gives a clear brown solution. 1 eq. KOTVu (potassium butoxide) is added with stirring, which after a few minutes leads to a clear solution. 1 equivalent of MeJ (methyl iodide) was added with a syringe and the solution was heated under reflux for 4 hours. The solution was then left under stirring overnight at room temperature. The next day, 50 ml of water are added and the mixture is extracted with 4x50 ml of methylene chloride. The resulting organic phases are combined, dried over magnesium sulfate and concentrated. The resulting harder substance is purified by flash chromatography on silica gel using 50/50 ethyl acetate / hexane to remove from the adsorbent. This results in 1.80 g of a white solid.

Yield 86% mp. 154-156 ^about S.

 Following the above procedure, however, when replacing phenylpyrrol-3-kaarbonitrile or 3-nitro-2- (substituted) phenylpyrrole not 4,5-dichloro-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile, the compounds described below are obtained (see table. 7).

 PRI me R 10. 1-benzyl-4,5-dibromo-2- (α α α-trifluoro-p-tolyl) pyrrole-2-carbonitrile.

In a 100 ml flask, 1.5 g of 4,5-dibromo-2- (α α α-tri fluoro-p-tolyl) pyrrole-3-carbonitrile is mixed with 50 ml of dry tetrahydrofuran, which leads to a clear dark solution. Add 1 equivalent of potassium butoxide with stirring. After a few minutes, the solution becomes clear. Benzyl bromide (0.65 g) is added via syringe. The mixture was refluxed overnight. The next day, thin layer chromatography (50/50 ethyl acetate / hexane) showed the presence of both starting materials and the product. The reaction mixture is treated as follows: 50 ml of water are added and the mixture is extracted with 4x50 ml of methylene chloride. The organic phases are combined and washed with 4x50 ml of a 10% aqueous sodium hydroxide solution. The organic phase is dried over magnesium sulfate and evaporated. This results in a brown solid that crystallizes from ethyl acetate with hexane. Yield 0.75% g40,7 T.pl.145-147 ^C. (decomposition).

 PRI me R 11. 4,5-dichloro-2- (3,4-dichlorophenyl) -1- (ethoxyphenyl) pyrrole-3-carbonitrile.

A sample of 4,5-dichloro-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile (1.0 g; 0.003 mol) is dissolved in 10 ml of dry tetrahydrofuran. Potassium tert-butoxide (0.37 g; 0.0033 mol, followed by chloromethyl ethyl ether (0.312 g; 0.0033 mol) was added to this solution. The mixture was stirred for about 1 h at room temperature, then poured into a large volume of water , precipitated product to precipitate. The white solid was collected and dried to give 1.0 g (91%), m.p. 128-130 ° ^C.

 PRI me R 12. 2-chloro-3-cyano-2- (p-chlorophenyl) pyrrole.

To a magnetically stirred at 20 ^C. a solution of 17.87 g (88.2 mmol, 1.00 equivalents) of 2- (p-chlorophenyl) -3-cyanopyrrole in 800 mL of dioxane was added dropwise 250.15 g 176.4 mmol; 2.00 equivalents of 5.25% by weight bleaching agent for 30 m. After an additional 30 minutes of stirring at room temperature, the reaction solution was poured into 2200 ml of water. The resulting mixture was filtered in vacuo, after which a small amount of black solid remained. The filtrate is acidified to pH2 conc. hydrochloric acid, which gives a brown solid. This solid was suction filtered and the collected solids were washed with water to give 22.41 g of a brown solid. This solid is treated with 100 ml of a 5% aqueous sodium hydroxide solution to dissolve the bulk of the remaining small amount of undissolved black solid. This black solid, dissolved in 100 ml of ethyl acetate, is washed each time with 75 ml of a 5% aqueous solution of sodium hydroxide, water and a saturated aqueous solution of sodium chloride. The ethyl acetate layer was dried (magnesium sulfate), treated with activated carbon, filtered, then evaporated in vacuo on a rotary evaporator, giving 1.10 g of 5.3% yield of an orange-brown solid. This solid was recrystallized from a mixture of ethyl acetate and chloroform, which afforded 0.51 g (2.5% yield) of an off-white solid 4-chloro-3-cyan- (p-chlorophenyl) pyrrole.

Mp 251-253 ^about S.

 PRI me R 13. Obtaining 5-bromo-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile.

A sample of 2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile (2.0 g; 0.008 mol) was dissolved in 100 ml of dioxane while heating to 40-50 ^C. The solution was then cooled ^to 30 ° C and bromine (1 , 3 g; 0.008 mol). After stirring for 1 h at room temperature, the solution was poured into water and a gray solid (2.2 g, 88%), mp. 233-236 ^{° C,} decomposition.

 PRI me R 14. Obtaining 5-bromo-4-chloro-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile.

A sample of 5-bromo-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile (0.158 g; 0.005 mol) was dissolved in tetrahydrofuran (5 ml). An equivalent amount of t-butyl hypochlorite was added and the solution was stirred overnight. The solution was poured into water and a precipitate was collected (0.052 g, 30%). Mp more> 275 ^about C.

 In a similar manner, 2-bromo-3-chloro-5- (3,4-dichlorophenyl) -4-nitropyrrole can be prepared starting from 2-bromo-5- (3,4-dichlorophenyl) -4-nitropyrrole.

 PRI me R 15. Obtaining 5-bromo-4-chloro-2- (p-chlorophenyl) pyrrole-3-carbonitrile.

To a magnetically stirred at 22 ^C. a solution of 0.17 g (0.67 mmol; 1.00 equivalents) of 4-chloro-2- (p-chlorophenyl) pyrrole-3-carbonitrile in 100 ml of chloroform was added dropwise over 30 minutes a solution of 0.20 ml (0.62 g; 3.88 mmol; 5.79 equivalents) of bromine in 5 ml of chloroform. Addition does not produce exothermic heat. After 3.25 hours of stirring at room temperature, the clear red reaction solution was evaporated in vacuo to give 0.28 g of an off-white solid. This solid is stirred up in a mixture of hexane and methylene chloride, which gives after vacuum filtration 0.23 g of an off-white fluffy solid. Mp 262-263 ^about C, decomposition.

 PRI me R 16. Obtaining 5-chloro-4-bromo-2- (p-chlorophenyl) -pyrrole-3-carbonitrile.

To a magnetically stirred at 45 ^C. a solution of 1.00 g (4.22 mmol; 1.00 eq) of 5-chloro-2- (p-chlorophenyl) pyrrole-3-carbonitrile in 300 ml of chloroform was added dropwise over 30 minutes a solution of 0.40 ml (1.24 g; 7.76 mmol; 1.84 equivalents) of bromine in 25 ml of chloroform. Addition is not accompanied by the release of exothermic heat. At the end of the addition, a small amount of solid precipitates. After 19.5 hours of stirring at room temperature, the reaction mixture was evaporated in vacuo to give 1.49 g of an orange-white solid. This solid is agitated in a mixture of hexane and methylene chloride, which after vacuum filtration gives 1.33 g (100% yield) of a fluffy white solid. Mp 250-258 ^{° C,} decomposition.

 PRI me R 17. Obtaining 5-chloro-2- (p-chlorophenyl) pyrrole-3-carbonitrile.

To a magnetically stirred at 35 ^C. a solution of 2.40 g (11.8 mmol, 1.00 equivalents) of 2- (p-chlorophenyl) pyrrole-3-carbonitrile and 65 ml of glacial acetic acid is added dropwise by syringe 0.75 ml (1.26 g; 9.35 mmol; 0.79 equivalents) sulfuryl chloride over 5 m. After about 5 m, after the addition is complete, a solid precipitates from the reaction solution. After 45 m stirring at room temperature, the reaction mixture was filtered and the collected solid was washed thoroughly with cold acetic acid. 2.08 g (74% yield on crude product) of an off-white solid are obtained. This substance is recrystallized from 75 ml of hot acetic acid, which gives 1.63 g (58% yield) of product 97 wt. degree of purity. Mp 258.5-261 ^about S.

 PRI me R 18. Obtaining 2- (3,4-dichlorophenyl) -1-methylpyrrole-3-carbonitrile.

 In a 100 ml flask, 2.0 g of 2- (3,4-dichlorophenyl) pyrrole-4-carbonitrile was dissolved in 50 ml of dry tetrahydrofuran and 1 equivalent of potassium t-butyllite was added. A slightly cloudy solution is obtained. Then, 1 equivalent of methyl iodide is pipetted to the mixture. This leads to poor color enlightenment. A drying tube is attached to the flask and left under stirring at ambient temperature overnight.

The next morning, a small amount of a slightly colored precipitate appears in the flask. Then 50 ml of water are added and the solution becomes transparent until a solid precipitates from the solution. This solid is filtered from the solution and compared with the starting material by thin layer chromatography (25% ethyl acetate / hexane). This showed the presence of a new single spot moving with greater speed than the starting material. Said solid was dried in a vacuum oven ^at 50 ° C overnight. Received 1.31 g of product (62% yield). Mp 140-142 ^about S.

 Example 19 Preparation of 4,5-dichloro-2- (3,4-dichlorophenyl) -1-methylpyrrole-3-carbononitrile.

 In a 50 ml round bottom flask, 0.5 g of 2- (3,4-dichlorophenyl) -1-methylpyrrole-3-carbonitrile is mixed with 35 ml of acetic acid. The mixture is slightly warmed with a “Fen” heat radiator to dissolve all of the pyrrole.

 To this clear solution add 2 equivalents of sulfuryl chloride with a pipette. The solution was left under stirring at room temperature for 12 hours.

After 12 hours, the solution was poured into 50 ml of water, which caused the appearance of a white precipitate. It is filtered off and dried in a vacuum oven at 50 ° C. ^for 3 hours.

 The obtained solid is identical, according to thin-layer chromatography (25% ethyl acetate-hexane) and infrared analysis of the product of example 9. The yield of the product is 0.36 (56%).

 PRI me R 20. Obtaining 4,5-dichloro-2- (3,4-dichlorophenyl) -1- (2-hydroxyethyl) -pyrrole-2-carbonitrile.

To a stirred mixture, 2.0 g (6.5 mmol) of 4,5-dichloro-2- (3,4-dichlorophenyl) pyrrole of 3-carbonitrile and 0.88 g (7.8 mmol) of potassium tert-butylate, heated with 0.98 g (7.8 mmol) of bromoethanol are added under reflux in 50 ml of dioxane. The mixture was stirred under reflux for 12 hours, cooled, diluted with 50 ml of water and extracted several times with chloroform. The combined chloroform extracts are dried over magnesium sulfate and concentrated in vacuo until a solid remains. From the composition of this substance, after heating and dissolving in ethyl acetate, most of the starting pyrrole precipitates upon cooling. Concentration of the mother liquor and recrystallization of the residual solid from 20% ethyl acetate in hexane gives 0.31 g of a white solid, mp. 143-145 ^about C; infrared analysis 5077A.

 PRI me R 21. Obtaining 4,5-dichloro-2- (3,4-dichlorophenyl) -pyrrole-1,3-dicarbonitrile.

Potassium t-butylate (617 mg, 55 mmol) is added portionwise to a solution of 3-cyano-4,5-dichloro 2- (3,4-dichlorophenyl) pyrrole (1.52 g; 5 mmol) in anhydrous tetrahydrofuran (20 ml) . After 30 m, a solution of cyanobromide (583 mg; 5.5 mmol) in tetrahydrofuran (1 ml) was added. The reaction mixture was kept at room temperature overnight. The solvent is removed in a rotary evaporator. The residue was taken up in water and extracted with ethyl acetate. The organic layer was washed with water and a saturated solution of sodium chloride, then dried under magnesium sulfate. Evaporation and crystallization of the residue from ethyl acetate gave white crystals (1.07 g); so pl. 250,5-252,0 ^C; infrared spectrum (nujol) 2255, 2245 cm ^-1 (CN);
¹³ C NMR (dimethyl sulfoxide-d ₆ ) 102.7 (N-CN); 113.7 (3-CN); mass spectrum 331.9 (M + 1).

 Example 22 Preparation of 4,5-dichloro-2- (3,4-dichlorophenyl) -1- (3-iodo-2-propynyl) pyrrole-3-carbonitrile.

To a stirred mixture of 1.91 g (5.5 mmol) of 4,5-dichloro-2- (3,4-dichlorophenyl) -1- (2-propynyl) pyrrole-3-carbonitrile in 500 ml of methanol add 69 ml of 10 % aqueous solution of sodium hydroxy. Then 0.70 g (2.7 mmol) of iodine. The mixture is stirred for 12 hours, then acidified and diluted with 200 ml of water. The precipitated solids are collected and recrystallized from methanol, which gives 0.51 g of white crystals, so pl. 115-116 ^about S.

 PRI me R 23. Obtaining 2- (3,4-dichlorophenyl) -4,5-diiodopyrrole-3-carbonitrile.

N-iodosuccimide (5.7 g; 0.0254 mol) is slowly added to a solution of 2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile (3.0 g; 0.0127 mol) in 100 ml of tetrahydrofuran. The reaction mixture was stirred for several hours at ²⁵ ° C until thin layer chromatography (silica gel; 100: 100: 1 ether: petroleum ether: acetic acid) do not show complete. The mixture is evaporated in vacuo to give a residue containing pyrrole and succinic acid imide, the crude solid is dissolved in 500 ml of ether and shaken with 5x400 ml of water to remove succinic acid imide. The ether layer was dried over sodium sulfate and evaporated in vacuo, which leaves 2.0 g (32.3%) of a tan solid with a melting point of more than 230 ^° C (leaves purple fumes).

 PRI me R 24. Obtaining 2-phenyl-1-pyrroline-4-carbonitrile.

A solution of acrylonitrile (0.65 ml; 0.01 mol) and N-trimethylsilyl) methyl-S-methyl-benzoltioimidata (2.4 g; 0.01 mol) in tetrahydrofuran (100 ml) was cooled to -5 ^{° C} in a bath acetone with ice. While purging with nitrogen, a solution of tetrabutylammonium fluoride (1.0 ml of a 1N solution in tetrahydrofuran) and tetrahydrofuran (20 ml) was added dropwise in 30 minutes. The solution was stirred for an additional 30 negative at minus 5 ^{° C,} then allowed to gradually warm to ambient temperature. Stirring is continued for another 18 hours, then allowed to gradually warm to ambient temperature. Stirring is continued for another 18 hours, then the solvent is removed under reduced pressure. The residue was partitioned between ether and water and the aqueous layer was extracted with fresh ether. The combined organic layer was washed with water, then with a saturated sodium chloride solution. The solution was dried over magnesium sulfate. Cooling of the filtrate causes the precipitation of an off-white solid (1.2 g; 70%) from the theoretical yield. The spectral characteristics of this substance are identical to those described in (J. Org. Chem. 52, 2523 (1987)).

Mp 95-97 ^about S.

 PRI me R 25. Obtaining 2-phenyl-pyrrole-4-carbonitrile.

When nitrogen was flushed with 2,3-dichloro-5,6-di-cyano-1,4-benzoquinone (0.23 g; 0.001 mol) and 2-phenyl-1-pyrroline-4-carbonitrile (0.17 g; 0.001 mol) is dissolved in 1,2-dimethoxyethane (13 ml) until a clear orange solution forms. Pyridine (0.08 ml; 0.01 mol) is added in a single portion, which causes weak heating (up to about 28 ^° C) due to the heat of the exothermic reaction and the immediate formation of a greenish-gray precipitate. The suspension was stirred at room temperature for 18 hours, during which time most of the solvent was evaporated. A brownish semi-solid residue was partitioned between ether and saturated sodium carbonate solution. The red-brown aqueous layer was extracted twice with ether. The combined ether layers were washed with fresh water, then with a saturated solution of sodium chloride. After drying over magnesium sulfate, the solvent is removed under reduced pressure, resulting in a white semi-solid. This material was recrystallized from ethylene chloride (DARCO treatment) to give pale purple crystals (0.1 g). Calculated: for C ₁₁ H ₈ N ₂ : C 78.57; H 4.76; N, 16.67; Found: C, 78.65; H 4.70; N, 16.43;
Mp 156-158 ^about S.

 PRI me R 26. Obtaining 2,4-dibromo-5-phenyl-pyrrole-3-carbonitrile.

While purging with nitrogen, a solution of bromine (0.6 ml; 0.012 mol in chloroform (5 ml) is added dropwise over 20 m to a stirred solution of 2-phenyl-pyrrole-4-carbonitrile (0.84 g; 0.05 mol) in chloroform ( 20 ml). The resulting solution was stirred for 18 h at room temperature, the solvent was removed under reduced pressure to give a solid which was recrystallized from ethylene dichloride (treatment A CO). The desired desired product was obtained (0.6 g), mp .239-242 ^about C.

By the methods described in examples 24, 25 and 26, 2,4-dibromo-5- (p-chlorophenyl) pyrrole-3-carbonitrile was also obtained. so pl. 270-272 ^{° C} (decomposition).

 PRI me R 27. 3 '4' -dichloro-3- (1,3-dioxolan-2-yl) propiophenone.

To a vigorously stirred mixture of magnesium turnings metal (0.64 g, 26 mmol) in 10 mL of tetrahydrofuran at ²⁵ ° C in 100 ml three-necked round bottom flask equipped with thermometer, 60 ml of the feed funnel and nitrogen inlet is added dropwise 2- (2 β-bromoethyl) -1,3-dioxalane (4.7 g, 26 mmol) in 40 ml of tetrahydrofuran. The rate of addition is adjusted so that the temperature was below 50 ^C. The reaction mixture was stirred for 1 h at 25 ^C. 120 ml tetrahydrate is mixed with potassium 3,4-dichlorobenzoate (5.0 g, 22 mmol) under a nitrogen blanket. The Grignard solution is then quickly removed by decantation from unreacted magnesium chips and added dropwise to the rapidly stirred suspension of potassium benzoate. The reaction mixture was stirred for 24 hours at 25 ° ^C. To the reaction mixture was added 50 ml of diethyl ether and 15 ml of 3 N hydrochloric acid and the layers separated. The organic layer was washed with a saturated aqueous solution of sodium bicarbonate for a neutral medium, and then washed once with 10 ml of brine. Drying over magnesium sulfate and evaporation in a rotary evaporator leads to a semi-solid, which is chromatographed on silica gel using 3: 1 hexaneethyl acetate to remove from the adsorbent, which gives keto-acetal (4.3 g; 60%) as a white solid so pl. 115-117 ^about S.

 PRI me R 28. Obtaining 3- (3,4-dichlorobenzoyl) propionaldehyde.

 10 g (26 mmol) of 3'4'-dichloro-3- (1,3-dioxolan-2-yl) propiophenone is added to 30 ml of 0.2 m oxalic acid (obtained by dissolving 0.9 g of oxalic acid dihydrate in 30 ml of water) and 5 ml of ethanol. The mixture was refluxed for 1 hour, then allowed to cool. Most of the ethanol is evaporated in a rotary evaporator; add 100 ml of diethyl ether, then 20 ml of a saturated solution of sodium bicarbonate. The layers are separated and the organic phase is dried over magnesium sulfate. Evaporation in a rotary evaporator results in a yellow viscous oil which, upon chromatography over silica gel using 3: 1 hexane-ethyl acetate, gives ketaaldehyde (6.3 g; 75%) as a white solid.

 PRI me R 29. Obtaining 2- (3,4-dichlorophenyl) pyrrole.

Ammonium acetate (4 g, 52 mmol) was added to a suspension of 3- (3,4-dichlorobenzoyl) propionialdehyde (6 g; 26 mmol) in 60 ml of absolute ethanol. The reaction mixture was refluxed for 20 m and allowed to cool. Most of the ethanol was evaporated in a rotary evaporator and 200 ml of 1: 1 dichloromethane diethyl ether was added, followed by 50 ml of water. The layers were separated and the organic phase was dried over sodium sulfate. Rotational evaporation gives a dark brown oil, which when chromatographed over silica gel and used to remove 3: 1 hexane-ethyl acetate from the adsorbent, shows: pyrrole (4.6 g, 83%) as a light brown solid, m.p. 49-51 ^about S.

 PRI me R 30. Obtaining 5- (3,4-dichlorophenyl) pyrrole-2-carboxaldehyde.

 To 10 ml of dimethylformamide, stirred under a nitrogen layer in a 50 ml round bottom flask, phosphorus oxychloride (0.6 ml; 6.5 mmol) is added dropwise via syringe. The solution becomes warm and acquires a light yellow color. It is stirred with 20 m of adding 2- (3,4-dichlorophenyl) pyrrole (1 g, 4.7 mmol in portions).

The beige suspension is stirred for 30 m, then heated ^to 50 ° C 40 m. To the cooled reaction mixture is added sodium acetate (10 g, 122 mmol) in 15 mL of water. The mixture is stirred for 20 m. The beige precipitate is filtered off from the reaction mixture and dried in air for 20 hours, which gives mostly pure aldehyde (1.1 g, 95%), mp. above 200 ^about C.

 PRI me R 31. Obtaining 5- (3,4-dichlorophenyl) pyrrole-2-carbonitrile.

To a suspension of 5- (3,4-dichlorophenyl) pyrrole-2-carboxaldehyde (1.5 g; 6.2 mmol) in 20 ml of water and 20 ml of ethanol is added hydroxylamine-0-sulfonic acid (0.7 g; 6.2 mmol). The reaction mixture was refluxed for 1 hour. During this time, a gray precipitate appeared. After cooling, the reaction mixture was filtered to give substantially pure nitrile (1.5 g, 99%) as a gray solid, mp. 170-171 ^about S.

 PRI me R 32. Obtaining 3,4-dibromo-5- (3,4-dichlorophenyl) pyrrole-2-carbonitrile.

To a solution of 5- (3,4-dichlorophenyl) pyrrole-2-carbonitrile (0.5 g, 2.1 mmol) in 20 ml of tetrahydrofuran under a layer of nitrogen, succinic acid N-bromide imide (0.8 g; 4) is added in portions. , 2 mmol). The reaction mixture was stirred at ²⁵ ° C for 30 m, then 10 ml of water and 40 ml of diethyl ether. The layers were separated and the organic layer was dried over sodium sulfate. Rotational evaporation followed by chromatography over silica gel using 3: 1 hexane ethyl acetate to remove from the adsorbent leads to dibromopyrrole (0.5 g, 60%) as a brown solid, mp over 250 ^about C.

 PRI me R 33. Obtaining 4-phenyl pyrrole-3-carbonitrile.

To a mixture of 5.0 g (39 mol) of succinic acid nitrile and 7.6 g (39 mmol) of (p-tolylsulfonyl) methyl isocyanide in 35 ml of dimethyl sulfoxide and 65 ml of ether, a suspension of sodium hydride (1.11 g; 46 mmol) in 80 ml of ether. The reaction mixture was kept under nitrogen for 1 h, then diluted with ether and water. The ether layer was separated, dried over magnesium sulfate and concentrated in vacuo. The resulting oil is chromatographed on silica gel using 1: 1 chloroform: ethyl acetate, which gives 2.5 g of a cream-colored solid. Recrystallization from ether with hexane afforded 1.15 g of material, mp. 123-125 ^about S.

Tetrahedron Letters 5337 (1972) mp. 128-129 ^about S.

 PRI me R 34. Obtaining 2,5-dichloro-4-phenylpyrrole-3-carbonitrile.

To a stirred mixture of 0.66 g (3.9 mmol) of 4-phenyl pyrrole-3-carbonitrile in 20 ml of dry tetrahydrofuran, cooled to 6 ^° C in an ice bath, 0.66 ml (1.11 g; 8 , 2 mmol) sulfuryl chloride 4 m. The mixture was kept at 5-10 ^{° C} an additional 45 m, followed by stirring for 30 m at a remote ice bath. The reaction mixture was poured into 80 ml of ethyl acetate and 40 ml of water. The organic phase is removed, washed with water and dried over sodium sulfate. Filtering through a short column, rinsing with ethyl acetate, and the concentration of the combined filtrates in vacuo gave 0.95 dark matter. Recrystallization from chloroform gives 0.42 g of off-white crystals, mp. 195-196 ^{° C} (and decomposition).

 Following the procedure of examples 33 and 34, receive the following analogues. For the synthesis of 2,6-dibromo-4- (p-chlorophenyl) pyrrole-3-carbonitrile, the procedure of Example 33 is followed using bromine in dioxane to replace sulfuryl chloride and tetrahydrofuran (see Table 8).

 PRI me R 35. Ethyl 4- (p-chlorophenyl) pyrrole-3-carboxylate.

To a mixture of 5.63 g of a 60% suspension of sodium hydride in oil in 200 ml of dry ether under nitrogen, a mixture of 23.5 g (122 mmol) of p-chlorocinnamate and 19.4 g (122 mmol) (p- tolylsulfonyl) methyl isocyanide in solution in 180 ml of ether and 80 ml of dimethyl sulfonide. The duration of the addition of about 20 m leads to a weak effect of the reflux condenser in the mixture. After an additional 10 m stirring, the mixture was diluted with 100 ml of water. The mixture was extracted 4 times with ether, which was then dried over magnesium sulfate, followed by concentration in vacuo. The resulting solid is recrystallized from ethylene dichloride, which gives 7.8 g of crystals, so pl. 137-138 ^about S.

 PRI me R 36. Obtaining 3- (p-chlorophenyl) -pyrrole.

 A mixture of 22.0 g of crude ethyl 4- (p-chlorophenyl) pyrrole-3-carboxylate after recrystallization of the mother liquor and recrystallized product from the previous step is stirred under reflux with 150 ml of a 2.5% aqueous solution of sodium hydroxide 2.5 h The mixture is cooled, extracted with ether and acidified to give a precipitate that weighs 11.6 g after collecting and drying.

A mixture of 10.5 g of acid in 100 ml of ethanolamine is heated under reflux for 3 hours. After cooling, the mixture is poured onto 400 ml of ice and the resulting mixture is extracted 4 times with chloroform. The chloroform solution, after drying over magnesium sulfate and treatment with activated carbon, was concentrated in vacuo, resulting in a brown solid. Chromatography on silica gel using 1: 1 ethyl acetate-hexane affords 4.0 g of a white solid, mp. 117-118 ^about S.

 PRI me R 37. Obtaining 3- (p-chlorophenyl) -pyrrole-2-carboxaldehyde.

 To a mixture of 0.86 g (12 mmol) of dimethylformamide in 10 ml of dichloroethane, maintained under nitrogen and cooled in an ice bath, 1.49 g (12 mmol) of oxalyl chloride in 10 ml of dichloroethane are added in 25 m. The ice bath is removed, the mixture stirred an additional 15 m and re-cooled in an ice bath. To this mixture was added 1.5 g (8.5 mmol) of 3- (p-chlorophenyl) -pyrrole in 25 ml of dichloroethane per 20 m. The ice bath was removed and after an additional 30 m of stirring, the mixture was poured into 50 ml of ice water with 6 ml of 50% sodium hydroxide. The resulting mixture was extracted with ether and chloroform. The combined organic mixture was dried over magnesium sulfate and concentrated in vacuo. Purification of the resulting solid by silica gel chromatography using 1: 1 ethyl acetate hexane afforded 0.63 g of an off-white solid. It is directly used to convert to 3- (p-chlorophenyl) pyrrole-2-carbonitrile.

 PRI me R 38. Obtaining 3- (p-chlorophenyl) -pyrrole-2-carbonitrile.

 A mixture of 0.63 g (3.1 mmol) of 3- (p-chlorophenyl) -pyrrole-2-carboxaldehyde in 10 ml of water is stirred and ice-cooled as 0.52 g (4.6 mmol) of hydroxyamine-0- is gradually added. sulfonic acid in 10 ml of water. After addition, the ice bath was removed and the mixture was heated 25 m.

The solid obtained after cooling, according to NMR, is a mixture of the product and the starting aldehyde. This mixture is reacted in the same manner with an additional amount of 0.49 (4.2 mmole) hydroxyl amine-0-sulfonic acid in a total volume of 30 ml of water. The mixture was cooled, the resulting solids were collected and purified by silica gel chromatography using 1: 1 ethyl acetate-hexane, which afforded 0.46 g of a pink solid, mp. 114-115 ^about S.

 PRI me R 39. Obtaining 4,5-dibromo-3- (p-chlorophenyl) -pyrrole-2-carbonitrile.

To a mixture of 0.40 g (2.0 mmol) of 3- (p-chlorophenylpyrrole) -2-carbonitrile in 25 ml of chloroform was added 0.63 g (4.0 mmol) of bromine. After 20 m, the precipitate formed is collected and recrystallized from ethyl acetate, which gives 0.21 g of pink crystals, so pl. more than 250 ^about C.

Analysis for C ₁₁ H ₅ Br ₂ ClCN Calcd. C 36.62; H 1.39; Br 44.38; Cl 9.85; N, 7.77; Found C 36.92; H 1.32; Br 44.62; Cl 9.88; N, 7.50.

 PRI me R 40. Obtaining ethyl 5-bromo-4- (p-chlorophenyl) pyrrole-3-carboxylate.

Ethyl 4- (p-chlorophenyl) pyrro-3-carboxylate (1.6 g; 0.0064 mol) was dissolved in tetrahydrofuran (40 ml). Bromimid succinic acid (1.14 g, 0.0064 mol) was added in small portions at 25-28 ^C. After addition is complete the solution is stirred overnight at room temperature. The solution was concentrated in vacuo and the solid residue was partitioned between water and ether. The ether layer was separated and dried over magnesium sulfate. Treatment of the ether extract gives 1.9 g (90%) of a white solid, which is purified by stirring with a mixture of 80/20 hexane with ethyl acetate. Insoluble solid (1.3 g; 62%) was collected. Mp 161-164 ^about S.

 PRI me R 41. Obtaining 5-bromo-4- (p-chlorophenyl) pyrrole-3-carboxylic acid.

Ethyl 5-bromo-4- (p-chlorophenyl) pyrrole-3-carboxylate 15 g; 0.045 mol) is added to 200 ml of 10% sodium hydroxy and the suspension is heated under reflux. After everything has dissolved, the mixture is cooled, filtered, and the filtrate acidified. A white precipitate (8.0 g, 58%) was collected and dried. The solid has a melting point of over 205 ^{° C} and NMR (d ₆ -dimetilsulfoksid) showed pyrrole proton at 7.52 (d). The mass spectrum also coincided with that for monobrominated compounds.

 PRI me R 42. Obtaining 2-bromo-3- (p-chlorophenyl) pyrrole.

5-bromo-4- (p-chlorophenyl) pyrrole-3-carboxylic acid (8.0 g; 0.026 mol) was added to aminoethanol (24 mL) and the suspension was gradually heated to 110-120 ^C and kept at this temperature for 1 hour The solution is cooled, poured into water and extracted with ether. The ether extract according to thin-layer chromatography (75/25, hexane / ethyl acetate) showed the main fast-moving spot and slower-moving minor component. Treatment of the ester left a dark solid (4.0 g, 56%) representing 2-bromo-3- (p-chlorophenyl) pyrrole, which was directly used to prepare 5-bromo-4- (p-chlorophenyl) pyrrole-2- carbonitrile.

 PRI me R 43. Obtaining 5-bromo-4- (p-chlorophenyl) pyrrole-2-carbonitrile.

A freshly prepared sample of 2-bromo-3- (p-chlorophenyl) pyrrole (4.0 g; 0.015 mol) was dissolved in dry dimethoxyethane (25 ml). Then, while maintaining the temperature below 25 ^{° C} is added chlorosulfonyl isocyanate (3.08 g; 0.022 mol). After stirring overnight, the solution was treated with dimethylformamide (6 ml) and stirred for 3 hours. Then, the solution was poured into water, whereby a brown solid formed (3.8 g, 90%). Dry column chromatography (80/20 hexane / ethyl acetate) gives 1.4 g (33%) of a white solid, mp. 202-204 ^about C.

Analysis for C ₁₁ H ₆ BrClN ₂ Calculated, C 46.90; H, 2.13; N, 9.95; Cl, 28.39; Br 12.61; Found, C 47.20; H 2.09; N, 9.80; Cl 12.36; Br 27.42.

 PRI me R 44. Obtaining 3,5 dibromo-4- (p-chlorophenyl) pyrrole-2-carbonitrile.

A sample of 5-bromo-4- (p-chlorophenyl) pyrrole-2-carbonitrile (2.2 g; 0.0078 mol) was dissolved in 30 ml of dry dioxane. The solution was heated with bromine (1.3 g; 0.008 mol) in dioxane (20 ml), then stirred overnight at room temperature. The reaction mixture is poured into water, which is accompanied by the precipitation of a tan solid (2.6; 92%). A portion (1.6 g) was purified by flash chromatography using 75/25 hexane / ethyl acetate, which afforded 0.8 g of a gray solid, mp. 191-194 ^about S.

 PRI me R 45. Obtaining 3- (3,4-dichlorophenyl) -4-nitropyrrole.

Sodium hydride (2.66 60% oil suspension, washed with dry ether; 66 mmol) is suspended in 150 ml of dry ether. To this mixture was added over 15 min a mixture of 12.0 g (: 6: 5.5 mmol) of 3,4-dichloro-β-nitrostyrene; 10.8 g (5.5 mmol) of (p-tolylsulfonyl) methyl isocyanide in 50 ml of dimethyl sulfoxide and 150 ml of ether. The mixture is stirred. 1.5 hours diluted with 150-200 ml of water and additionally with ether. The ether layer was separated, dried over magnesium sulfate and concentrated in vacuo. The resulting 10.6 g of crude product is purified by chromatography on silica gel using a 4: 1 mixture of chloroform and ethyl acetate. 7.2 g of a solid fraction were recrystallized from chloroform-ethyl acetate-hexane to give 3.0 g of a yellow solid, mp. 187-188 ^о С Э (decomposition).

 PRI me R 46. Obtaining 2,5-dichloro-3- (3,4-dichlorophenyl) -4-nitropyrrole.

To a mixture of 3- (3,4-dichlorophenyl) -4-nitropyrrole (2.5 g; 9.7 mmol) in 200 ml of chloroform, heated to about 40 ^° C, 2.95 g (22 mmol) are added in 1 min. sulfuryl chloride. After another 1 h, the mixture was diluted with 100 ml of a saturated solution of sodium bicarbonate and 300 ml of ether. The organic layer was separated and dried over magnesium sulfate. After concentration in vacuo, a brown solid remains, which is chromatographed on silica gel using 4: 1 chloroform-ethyl acetate. The orange solid fraction was recrystallized from chloroform, then rechromatographed on silica gel using 4: 1 chloroform ethyl acetate, which afforded 0.36 g of a yellow solid, mp. 193-194 ^about S.

Also prepared according to the above methods of examples 45 and 46 2,5-dichloro-2-nitro-4-phenylpyrrole, so pl. 193-194 ^about C (decomposition).

 PRI me R 47. Obtaining 5- (p-chlorophenyl) pyrrole-2,4-dicarbonitrile.

A sample of 2-p-chlorophenyl-3-cyanopyrrole prepared according to the method of Example 4 (3.0 g; 0.015 mol) is dissolved in 50 ml of dry dimethoxyethane. Chlorosulfonyl isocyanate (3.39 g; 0.024 mol) is added to this solution. The addition is accompanied by an exothermic reaction, which requires some cooling. After 3 hours of stirring at room temperature, dimethylformamide (6-7 ml) was added and the solution was stirred for another 4 hours. The solution was poured into water. A white solid (3.4 g, 100%) precipitated. A sample (1.0 g) was purified by dissolving in ethyl acetate and passing the solution through a 60 ml flow-through filter funnel filled with silica gel. The filtrate was concentrated to give 0.7 g of a white solid, mp. 235-240 ^about C.

 Following the procedure of example 47, receive the following analogues (see table. 9).

 PRI me R 48. Obtaining 2-bromo-5- (p-chlorophenyl) pyrrole-3,4-dicarbonitrile.

A sample of 5- (p-chlorophenyl) pyrrole-2,4-dicarbonitrile (1.0 g, 0.004 mol) is dissolved in 20 ml of dioxane and a solution of bromine (0.8 g; 0.005 mol in dioxane (10 ml) is added to the solution. The solution was stirred for several hours at room temperature, then poured into water, which is accompanied by precipitation of a white solid (1.2 g, 100%). The solid has a melting point in excess of 225 ° ^C. The mass spectrum of the sample has a lattice that matches with desired structure.

 Following the procedure described in example 48, receive the following additional compounds (see tab. 10).

 PRI me R 49. Obtaining bromofumaronitrile.

 While purging with nitrogen, fumaronitrile (15.6 g; 0.2 mol in chloroform (150 ml) is heated under reflux, resulting in a clear solution. A solution of bromine (5.3 mol; 0.2 mol) in chloroform (25 ml ) is added dropwise over 30 minutes, this leads to a gradual discoloration, acidic (according to pH indicator paper) being released. The solution is heated under reflux for another 90 m. During this time, most of the color disappears. The solution is cooled and the solvent is removed under reduced pressure. amber oil (approximately theoretical weight To bromfumaronitrila).

The oil is subjected to distillation (0.2 mm RT.article) "drop by drop". The temperature is maintained below 120 ^{° C} (above this temperature there is rapid degradation of the material). A semi-solid is obtained, which transforms into an amber-colored waxy solid, mp. 43-47 ^about S.

 PRI me R 50. Obtaining 2-phenyl-pyrrole-3,4-dicarbonitrile.

While purging with nitrogen, a solution of bromofumaronitrile (4.7 g; 0.03 mol) and N- (trimethylsilyl) methyl-S-methyl-benzene-thiomidate (7.1 g. 0.03 mol) in hexamethylphosphoramide (HFA) was stirred at room temperature. Water (1.6 ml; 0.09 mol) is added in a single portion, washed with GMF (10 ml). The solution heats up almost immediately due to the heat of the exothermic reaction. The temperature quickly reaches 100 ^° C before dropping. The resulting dark red solution is continued to stir at ambient temperature for 20 hours. The reaction mixture is poured onto a mixture of ice and water, this leads to a gummy material, which gradually turns into a state from the separated parts of a beige solid. This material is collected by filtration and washed with cold water and dried.
A sample of 5- (p-chlorophenyl) pyrrole-2,4-dicarbonitrile (1.0 g, 0.004 mol) is dissolved in 20 ml of dioxane and a solution of bromine (0.8 g; 0.005 mol in dioxane (10 ml) is added to the solution. The solution was stirred for several hours at room temperature, then poured into water, which is accompanied by precipitation of a white solid (1.2 g, 100%). The solid has a melting point in excess of 225 ° ^C. The mass spectrum of the sample has a lattice that matches with desired structure.

 Following the procedure described in example 48, receive the following additional compounds (see tab. 10).

 PRI me R 49. Obtaining bromofumaronitrile.

 While purging with nitrogen, fumaronitrile (15.6 g; 0.2 mol in chloroform (150 ml) is heated under reflux, resulting in a clear solution. A solution of bromine (5.3 mol; 0.2 mol) in chloroform (25 ml ) is added dropwise over 30 minutes, this leads to a gradual discoloration, acidic (according to pH indicator paper) being released. The solution is heated under reflux for another 90 m. During this time, most of the color disappears. The solution is cooled and the solvent is removed under reduced pressure. amber oil (approximately theoretical weight To bromfumaronitrila).

The oil is subjected to distillation (0.2 mm RT.article) "drop by drop". The temperature is maintained below 120 ^{° C} (above this temperature there is rapid degradation of the material). A semi-solid is obtained, which transforms into an amber-colored waxy solid, mp. 43-47 ^about S.

 PRI me R 50. Obtaining 2-phenyl-pyrrole-3,4-dicarbonitrile.

While purging with nitrogen, a solution of bromofumaronitrile (4.7 g; 0.03 mol) and N- (trimethylsilyl) methyl-S-methyl-benzene-thiomidate (7.1 g; 0.03 mol) in hexamethylphosphoramide (HFA) was stirred at room temperature. Water (1.6 ml; 0.09 mol) is added in a single portion, washed with HMPA (10 ml). The solution heats up almost immediately due to the heat of the exothermic reaction. The temperature quickly reaches 100 ^° C before dropping. The resulting dark red solution is continued to stir at ambient temperature for 20 hours. The reaction mixture is poured onto a mixture of ice and water, this leads to a gummy material, which gradually turns into a state from the separated parts of a beige solid. This material was collected by filtration and washed with cold water and dried on a filter. After further drying (vacuum drying oven) at ⁶⁰ ° C, the material was recrystallized twice from ethylene dichloride (DARCO treatment), resulting in a white powder.

Analysis for C ₁₂ H ₇ N ₃
Calculated With 74.61; H 3.63; N, 21.76;
Found C, 74.45; H 3.84; N, 21.61.

Mp 197-200 ^about S.

 PRI me R 51. Obtaining 2-bromo-5-phenylpyrrol-3,4-dicarbonitrile.

When nitrogen was flushed, 2-phenyl-pyrrole-3,4-dicarbonitrile (1.4 g; 0.0075 mol) was added to chloroform (35 ml), which dissolved most of the solid. A solution of bromine (0.4 ml; 0.008 mol) in chloroform (5 ml) is added dropwise over 20 minutes. Initial staining disappears quickly, however, as the precipitation of a new, resinous solid begins, the stain remains. After 30 m stirring at room temperature, the mixture begins to heat under reflux, which leads to the formation of a solid substance consisting of much more discrete fragments. After 90 m heating under reflux, the reaction mixture was cooled and the determined portion was removed and analyzed by high pressure liquid chromatography (HPLC). It is shown that about 60% of the starting material remained unchanged. Fresh bromine (0.2 ml; 0.004 mol) was added in a single portion and heating under reflux was continued for an additional 45 m, after which 10% of the starting material was found in a certain largest part. Another portion of fresh bromine (0.2 ml; 0.004 mol) was added to the suspension heated under reflux, and heating under reflux was continued for an additional 30 m. The suspension was cooled and stirred for 18 hours at room temperature. The solvent was removed under reduced pressure to give a greenish solid, which was extracted with hot chloroform. As a result, a dark substance remains. The extract is treated according to the DARCO method and filtered hot. A clear yellow filtrate quickly begins to precipitate a white precipitate. After cooling to minus 10 ^° C, a white solid was collected by filtration.

Analysis for C ₁₂ H ₆ BrN ₃ Calculated, C 52.94; H 2.21; N, 15.44; Br 29.41; Found, C 51.64; H 2.35; N, 14.91; Br 28.69.

Mp 225-258 ^about S.

 PRI me R 52. Obtaining 2 (3,4-dichlorophenol) -5-nitropyrrole-3-carbonitrile.

2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile (3.0 g; 0.013 mol) is added to acetic anhydride (50 ml) and 90% nitric acid (0.6 ml), and very slight exothermic heat. The mixture was slowly warmed to 30 ^{° C,} then maintained at 30-33 ^C until everything goes into solution. A new solid is gradually precipitated. The mixture was stirred for 2 to 3 hours at room temperature, then poured into water and ice to decompose acetic anhydride. After 1 hour of stirring, the mixture was filtered, the solid was collected (2.9 g, 82%) and dried. A portion (1.5 g) was purified by silica gel column chromatography using 75/25 hexane and ethyl acetate to remove it from the adsorbent, which afforded 0.7 g of a yellow solid with mp. 228-231 ^about S.

Analysis for C ₁₁ H ₅ Cl ₂ N ₃ O ₂ : Calculated C 46.80; H 1.77; N, 14.89; Cl 25.17; Found C, 46.50; H 1.96; N, 14.27; Cl 24.30.

According to the same procedure, starting from 2- (p-chlorophenyl) pyrrole-3-carbonitrile, 2- (p-chlorophenyl) -5-nitropyrrole-3-carbonitrile is obtained, m.p. 201-206 ^{° C,} as 2- (p-trifluoromethylphenyl) pyrrole-3-carbonitrile gives 2- (p-trifluoromethyl phenyl) -5-nitropyrrole-3-carbonitrile Following the above procedure. This connection has a so pl. 164-165.5 ^about S.

 Example 53. Preparation of 4-bromo-2- (3,4-dichlorophenyl) -5-nitro-pyrrole-3-carbonitrile.

2- (3,4-dichlorophenyl) -5-nitropyrrole-3-carbonitrile (0.5 g; 0.0017 mol) was dissolved in dry dioxane (10 ml). To this solution was added bromine (0.28 g; 0.0017 mol) in dioxane. After stirring overnight, the solution was poured into water, which was accompanied by the precipitation of a tan solid (0.54 g, 88%). Recrystallization from acetonitrile (5 ml) gives 0.26 g of a tan solid with a melting point of 195-200 ^about S.

Analysis for C ₁₁ H ₄ BrClN ₃ O _2: Calculated C 36.57; H 1.10; N, 11.63; Br 22.13; Cl 19.67; Found C, 36.46; H 1.29; N, 11.50; Br 21.63; Cl 19.28.

Following the procedure of Example 53 above, however, starting from 2- (p-chlorophenyl) -5-nitropyrrole-3-carbonitrile, 4-bromo-2- (p-chlorophenyl) -5-nitro-pyrrole-3-carbonitrile was obtained, t .pl. 180-185 ^about S.

 PRI me R 54. 5- (3,4-Dichlorophenyl) -4-nitropyrrole-2-carbonitrile.

To a suspension of 5- (3,4-dichlorophenyl) pyrrole-2-carbonitrile (1.2 g; 5.1 mmol) in 25 ml of acetic anhydride at ³⁰ ° C was added dropwise 90% nitric acid under a nitrogen blanket (0, 3 ml; 5.1 mmol). The reaction mixture is heated by an exothermic reaction to 45 ^° C and becomes a green solution. After 2 hours of stirring, the reaction mixture was poured into 50 ml of water and stirred vigorously for 5 m. The resulting beige precipitate was filtered off and dissolved in a minimum amount of acetone. Chromatography over silica gel using 3: 1 hexane with ethyl acetate gave nitropyrrole (1.2 g; 84%) as an off-white solid, mp. more than 200 ^about C.

 PRI me R 55. 3-bromo-5- (3,4-dichlorophenyl) -4-nitropyrrole-2-carbonitrile.

To a suspension of 5- (3,4-dichlorophenyl) -4-nitropyrrole-2-carbonitrile (0.6 g; 2.1 mmol) in 10 ml of dioxane at 25 ° ^C. under nitrogen was added dropwise a solution of bromine (0.3 g; 2.1 mmol) in 5 ml of dioxane. The reaction mixture was stirred overnight. Adding 50 ml caused precipitation of a yellow solid which was collected and dried in a vacuum oven (50 mm Hg, 45 ^C) to afford the brominated pyrrole (0.7 g; 90%) as a yellowish solid, m.p. . over 200 ^about C.

 PRI me R 56. 4- (p-chlorophenyl) -2- (trifluoromethyl) -2-oxazolin-5-one.

Trifluoroacetic anhydride (1.7 ml; 0.012 mol) was added portion-once to the powdered 2- (p-chlorophenyl) glycine (11.4 g; 0.06 mol), causing an immediate warming to about 40 ^{° C} due to the exothermic reaction, moreover, a yellow coloration appears on the surface of the solid. As the mixture is gradually heated to 70 ^° C, most of the solid is dissolved to an orange-amber oil. All the solid is dissolved in 2 hours. Heating is continued for another 1 hour. The solvent is removed under reduced pressure in a rotary evaporator. Toluene is added twice and removed under reduced pressure, however, the smell of trifluoroacetic acid is still apparent. This yellow semi-solid substance (theoretical yield); the degree of purity exceeds 90% according to high pressure liquid chromatography (HPLC) represents the compound identified above. Apply it to the next step without further purification.

 Example 57. Preparation of 2- (p-chlorophenyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile.

4- (p-chlorophenyl) -2- (trifluoromethyl) -2-oxazolin-5-one (2.5 g; 0.01 mol) was dissolved in nitromethane (50 ml). To the solution, 2-chloroacrylonitrile (8.0 ml; 0.10 mol) was added in a single portion, and the resulting solution was stirred for 18 hours under reflux under a nitrogen atmosphere. Cooling the red-brown solution to minus 5 ^° C in an ice bath with acetone causes the formation of a precipitate, which is collected by filtration and washed with a small amount of cold nitromethane. The resulting tan solid was recrystallized from hot dichloroethane to give the product as white crystals (1.8 g, 56% of theory), mp 238-241 ^{° C} (decomposition).

 By using a suitable arylglycine in the procedure of Example 55, following the procedure of this Example, the following 2-aryl-5- (trifluoromethyl) pyrrole carbonitriles are prepared (see Table 11).

 PRI me R 58. Obtaining 4-bromo-2- (p-chlorophenyl) -5- (trifluoro) 4-methyl) pyrrole-3-carbonitrile.

While blowing with nitrogen, a suspension of 2- (p-chlorophenyl) -5- (trifluoromethyl) pyrrole-5-carbonitrile (1.6 g, 0.005 mol) in acetic acid (25 ml) was heated at ⁶⁰ ° C until all material is dissolved with the formation of a clear solution. A solution of bromine (0.8 ml; 0.015 mol) in acetic acid (10 ml) is added dropwise over 15 m to a solution heated under reflux. The solution was heated in this way for 6 hours, then stirred for 18 hours. At room temperature, liquid chromatography carried out under elevated pressure of the reaction mixture showed an approximately 80% conversion to product. The mixture is again heated to reflux and a greater amount of bromine (0.5 ml; 0.01 mol) in acetic acid is added dropwise. After further heating under reflux (3 h), the selected amount showed a 95% conversion to product. The reaction mixture was cooled, the solvent was removed under reduced pressure on a rotary evaporator to give a dark gray solid. Toluene was added to the mixture and removed under reduced pressure, but the smell of acetic acid still remained. All material is dissolved in hot toluene (75 ml), and a cloudy solution forms, which is treated on a DARKO filter and filtered. After cooling the pinkish solution to room temperature, a white solid is released. After cooling in the freezer, the solid is collected by filtration, washed with hexanes and dried on the filter. Additional drying in a vacuum oven at 45 ^about C led to the product (1.2 g, approximately 60% of theory). T. pl. 247-250 ^{° C} (decomposition).

Analysis for C ₁₂ H ₅ BrClF ₃ N ₂ Calculated: C 41.20; N 1.43; N, 8.01; Br 22.89; Cl 10.16; F 16.31; Found C, 41.27; H 1.48; N, 8.10; Br 22.92; Cl 10.16; F 16.03.

 By brominating the appropriate 2-aryl-5- (trifluoromethyl) pyrrole-3-carbonitrile obtained according to the procedure of Example 57, respectively, according to the above recipe, the following compounds are prepared (see table 12).

 Example 59. Preparation of 2- (4-chlorophenyl) -5-trifluoromethyl-pyrrole-3,4-dicarbonitrile.

Trifluoroacetic anhydride (3.1 ml; 0.22 mol) is added in a single portion to (4-chlorophenyl) glycine (2.0 g; 0.011 mol), which causes an immediate yellow stain and slight phlegm. The mixture is gradually heated to reflux, which causes the dissolution of all material to a yellowish-orange solution, which is further heated for 2 hours. The reaction mixture is cooled and the solvent is removed under reduced pressure. Toluene is added twice, followed by its removal under reduced pressure, which leads to a very thick oil (V _co = 1800 cm ^-1 ). This residue was dissolved (some insoluble matter remained) in nitromethane (40 ml) and bromofumaronitrile (2.7 g; 0.018 mol) was added in a single portion. The resulting solution was heated under reflux for 18 hours to give a dark red solution. The solvent was removed under reduced pressure and the dark residue was dissolved in dichloroethane. A certain amount of insoluble matter is removed by filtration.

The material was fractionated by dry column chromatography (silica gel, 3% 2-Pr OH in dichloroethane) and the appropriate fractions were collected. Evaporation of one fraction gave the title compound as a yellow solid, which was recrystallized from nitromethane (Darco treatment) to give a pale yellow solid (0.2 g) t.pl.238-241 ^C (some decomposition).

 PRI me R 60. p-Chloro-β- (formylmethyl) amino / nitrile of cinnamic acid, diethyl acetal.

A solution stirred with a magnetic stirrer of 250.0 g (1.39 mol) of p-chlorobenzoyl acetonitrile, 203 ml (185.9 g; 1.39 mol) of 2.2 diethoxyethylamine and 1300 ml of dried toluene is heated under reflux for 20 hours. Water ( 23.8 ml; 95.2% of theory) are collected in a Dean-Stark trap. A hot, cloudy dark brown solution with a large amount of undissolved solids is filtered off, using diatomaceous earth as an aid. After dilution with 200 ml of ethyl acetate, the solution was filtered through a 7 cm x 13.5 cm column of silica gel. The filtrate was concentrated in vacuo to give 354.3 g (86.4% yield on crude material) of a clear dark oil that gradually solidified. This solid was recrystallized from hot cyclohexane to give 324.2 g (79.1% yield) of a waxy orange solid. The NMR of this product showed the presence of an isomeric mixture of 78% (Z) and 23% (E) p-chloro-β- (formylmethyl) amino / nitrile of cinnamic acid, diethylacetal, so pl. 60-72 ^about S.

Following the above procedure, however, when replacing with appropriate benzoyl acetyl acetonitrile p-chloro-benzoyl acetonitrile and / or proper 2,2-di (C ₁ -C ₄ alkoxy) ethylamine 2,2-diethoxyethylamine, the following compounds are obtained (see table 13).

 PRI me R 61. 2- (p-chlorophenyl) -pyrrole-3-carbonitrile.

To 108 ml of trifluoroacetic acid was stirred at ²³ ° C, is added 54.00 (0.183 mol) of solid p-chloro-β - ((formyl-methyl) amino) cinnamyl nitrile diethylacetal for more than 45 m This addition increases the temperature to 38 ^o C due to an exothermic reaction and after 32 m during the addition, precipitation of a solid begins. After 30 m stirring at room temperature, the reaction mixture was filtered under vacuum and the collected solid was washed first with trifluoroacetic acid, then with a mixture of ethyl acetate and hexane, finally with hexane. The yield of an off-white solid was 16.83 g (45.4%), mp. 165-166 ^about S.

 Using the above procedure, but when replacing conc. hydrochloric acid to trifluoroacetic acid receive the following compounds (see tab. 14).

 PRI me R 62. 4,5-dichloro-2- (p-chlorophenyl) pyrrole-3-carbonitrile.

To a mechanically stirred solution of 16.83 g (83.1 mmol) of 2- (p-chlorophenyl) pyrrole-3-carbonitrile in 450 ml of glacial acetic acid at 36 ^{° C} was added dropwise 14.7 mL (24.70; 183.0 mmol of sulfuryl chloride in 18 m. The addition is accompanied by a slight exothermic temperature rise to 39 ^C. after an additional 16 m, the reaction mixture was vacuum filtered. The collected solids are washed first with acetic acid, then with water. The solid was recrystallized from hot ethyl acetate it has m. pl. 259-261 ^about S.

 PRI me R 63. 4,5-dibromo-2- (α α α-trifluoro-p-tolyl) pyrrole-3-carbonitrile.

To a stirred mixture of 0.8 g of 2- (α α α-p-tolyl) pyrrole-3-carbonitrile in 70 ml of chloroform was added 2 ml of bromine. After stirring overnight, a white solid precipitated from the mixture, which was collected by filtration. Thin layer chromatography (1: 1 ethyl acetate-hexane) showed the presence of only one component, so pl. more than 230 ^about C.

 Following the above procedure, but replacing properly substituted phenylpyrrole-3-carbonitrile 2 (α α α-trifluoro-p-tolyl) pyrrole-3-carbonitrile, the following compounds are obtained (see table 15).

PRI me R 64. α- (2,2-diethoxyethylamino) - β-nitrostyrene 3-nitro-2-phenylpyrrole. Alpha nitro acetophenone (5.7 g; 0.0345 mol) is added to 100 ml of toluene and 4.6 g (0.0345 mol) of amino acetaldehyde diethyl acetal are added. The reagents are placed in a 250 ml round bottom flask equipped with a Dean-Stark trap. The trap is filled with 4A molecular sieves. The mixture was refluxed for 18 hours. Toluene was removed in vacuo to give 8.36 g of α- (2,2-di-ethoxyethylamino) -β-nitrostyrene in the form of a brown oil. To this oil is added 50 ml of concentrated hydrochloric acid. As the flask is stirred, the oil turns into a yellow suspension. After 10 m, the solid was filtered off to give 2.48 g of a yellow solid. Recrystallization from ether (ethyl acetate) hexane will give 2 fractions of the product: 2.08 g with so pl. 190-192 ^about C (31%).

Max. 1485 cm ^-1 (NO ₂ );
H-NMR (deuterated chloroform / dimethyl sulfoxide). δ 6.73 (m, 2H); δ 7.46 (multiplet, 5H).

Other nitrostyrene derivatives can be prepared by the above reaction by replacing nitro acetophenone with a properly substituted α-nitro acetophenone and / or amino acetaldehyde diethyl acetal with suitable 2,2-di (C ₁ -C ₄ alkoxy) ethylamine, which leads to the following compounds (see table 16).

 PRI me R 65. 3-Dichloro-4-nitro-5-phenylpyrrole.

A mixture of 3-nitro-2-phenylpyrrole (1.56 g; 0.0083 mol) in 60 ml of dioxane is cooled in an ice bath as 25.9 g (0.0182 mol) of commercially available sodium hypochloride are added dropwise. After 45 m stirring, the mixture was acidified with concentrated hydrochloric acid. Water and diethyl ether are added. The layers were separated and the upper organic was washed with water, dried over anhydrous magnesium sulfate and concentrated in vacuo to give 2.21 yellow solid. Purification by chromatography using silica gel and a mixture of ethyl acetate and hexane in increasing ratios to remove from the adsorbent gives, after evaporation, 0.77 g of a yellow solid (36%), mp 190-190.5 ^about S.

 PRI me R 66. Obtaining 3-cyano-2- (3,4-dichlorophenyl) -N, N-dimethylpyrrole-1-carboxamide.

 A solution of 2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile (10.0 g, 0.0422 mol) in tetrahydrofuran was treated with potassium t-butoxide (13.2 g, 0.1176 mol), stirred at room temperature for one hour, then treated with dimethylcarbamyl chloride (13.2 ml, 15.31 mol), stirred at room temperature for 16 hours, treated with additional portions of potassium tert-butoxide (4.4 g, 0.0392 mol) and chloride dimethylcarbamyl (4.4 ml, 5.104 mol), heated at condensation temperature in the reflux condenser for one hour, cooled to room temperature temperature and poured into ethyl acetate and water.

The phases were separated and the organic phase was washed with water, dried over anhydrous magnesium sulfate and concentrated in vacuo to an oily residue. The oily liquid was purified by flash chromatography using silica gel and a 50:50 mixture of diethyl ether and hexanes as an eluent, whereby the title product was obtained as a white substance weighing 4.7 g (yield 36%), mp 120-122 ^about S.

 PRI me R 67. Obtaining N, N-dimethyl-2,3-dibromo-4-cyano-5- (3,4-dichlorophenyl) pyrrole-1-carboxamide.

A solution of N, N-dimethyl-3-cyano-2- (3,4-dichlorophenyl) pyrrole-1-carboxamide taken in an amount of 1 g in tetrahydrofuran was treated with bromine taken in an amount of 3.8 g, stirred for five days and concentrated in vacuo to give a brown oily liquid as a residue. The liquid was purified by chromatography using silica gel and a mixture of ether and hexanes as an eluent at a ratio of 1: 1, resulting in a semi-solid, which was pressed on a clay plate to form the title product as a white solid, the amount of which was 0.45 g; so pl. 144-149 ^about S.

 Example 68. Preparation of 4-bromo-1- (bromomethyl) -2- (p-chlorophenyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile.

A solution of 4-bromo-2- (p-chlorophenyl) -1- (methyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile (30 g, 0.0825 g mole) in carbon tetrachloride (450 ml) was treated bromine (13.2 mL, 18.8 g) and subjected to photolysis, influencing light from a mercury arc lamp in a photochemical reactor of 500 ml at 77-78 ^{° C} for 23 hours. to the reaction mixture was added bromine (4.4 mL , 0.0425 mol), and irradiation was continued for another 47 hours. The reaction mixture was subsequently washed with an aqueous metabisulfite solution and water and concentrated in vacuo to give a solid. This solid was triturated with carbon tetrachloride (50-60 ml) and heptane (100 mL) and filtered to give the title product as a white solid (18.3 g, m.p. 131-131,5 ° ^C).

 Example 69. Preparation of 4-bromo-2- (p-chlorophenyl) -1- (ethoxymethyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile.

 To 1000 ml of dry tetrahydrofuran was added 130.8 g of 4-bromo-2- (p-chlorophenyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile. The mixture was stirred, and 43.3 g of potassium tert-butoxide was added in several portions, which led to an exothermic reaction. The temperature of the exothermic reaction was controlled by cooling the reaction flask in a water bath.

 To the stirred mixture, 36.5 g of chloromethylethyl ether were added in two portions. Then, the progress of the reaction was monitored by thin layer chromatography.

After about four hours, the reaction mixture was diluted with 300 ml of ether and washed with dilute hydrochloric acid and water. The organic phase was separated, dried over magnesium sulfate, filtered and concentrated in vacuo to give 122 g of the title product. Recrystallization from 500 ml of isopropyl alcohol gave 102 g of the title product, which was a colorless solid with a melting point of 99-100 ^about C.

 PRI me R 70. Obtaining 4,5-dichloro-2- (3,4-dichlorophenyl) -1- (1-ethoxy-ethyl) pyrrole-3-carbonitrile.

To 4,5-dichloro-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile (5.0 g, 0.016 mol) dissolved in 300 ml of tetrahydrofuran, potassium tert-butoxide (2.75 g, 0.025) was added portionwise. praying), doing this while cooling with ice, and stirred. The cooled mixture was treated with a solution of 1-chloroethylethylether simple ester (2.31 g, 0.021 mol) in 15 mL of tetrahydrofuran at ¹⁰ ° C over a period of time is 5 min. The mixture was stirred for 30 minutes at ambient temperatures, evaporated to a volume of 50 ml and poured into a mixture of 200 ml of ethyl acetate and 100 ml of water. The organic layer was separated, washed with water (2 times in 100 ml), exposed to a solution of sodium chloride (1 time in 100 ml), dried over anhydrous magnesium sulfate and evaporated to obtain the title product, the amount of which was 5.9 g; so pl. 124-126 ^about S.

 PRI me R 71. Obtaining p-chloro-N - [(phenylsulfonyl) methyl] thiobenzamide.

Sodium benzosulfinate (17 g, 0.1 ml) was dissolved in 100 ml of water and treated with an aqueous solution of formaldehyde (3.2 g, 0.11 mol, 37%) and p-chlorothiobenzamide sludge (17.0 g, 0.1 mole) in 88% formic acid (100 ml). After stirring for 4.5 hours at 80-90 ^C. The reaction mixture was cooled. The solid was separated by draining the liquid above it; the solid was then treated with ethyl acetate, dried over magnesium sulfate and concentrated in vacuo to give 20.7 g (64% yield) of a yellow solid. A portion of this solid (17 g) was recrystallized from methanol to obtain 6.7 g of a yellow solid, which was then purified to a slurry in a solution of hexane in ethyl acetate taken in a ratio of 75:25, whereby the title product was obtained in an amount of 5 7 g with a yield of 20.9% mp 145-150 ^about C.

 PRI me R 72. Obtaining methyl p-chloro-N - [(phenylsulfonyl) methyl] thiobenzimidate.

A solution of p-chloro-N - [(phenylsulfonyl) methyl] thiobenzamide (1.0 g, 0.003 mol) in methylene chloride was cooled below 10 ^{° C,} treated with methyl trifluoromethanesulfonate (0.57 g, 0.0035 mol), stirred for three hours at a temperature of less than 10 ^about C and for 16 hours at room temperature and filtered. The filtrate was washed successively with water and a dilute potassium carbonate solution, dried over magnesium sulfate and concentrated in vacuo to give an oily residue that solidified. The residue was subjected to flash chromatography using methylene chloride and then a 90:10 mixture of methylene chloride and ethyl acetate, which played the role of eluents, resulting in the title product as a white solid, the amount of which was 0.4 g upon exit 40% mp 120-123 ^about S.

 PRI me R 73. Obtaining 2- (p-chlorophenyl) -4- (trifluoromethyl) pyrrole-3-carbonitrile.

A mixture of dimethoxyethane (15 ml) and dimethyl sulfoxide (5.5 ml) was treated with 60% sodium hydride (0.28 g). Then, all at once was added to a solution of methyl p-chloro-N - [(phenylsulfonyl) methyl] thiobenzimidate (1.07 g, 0.003 mol) and 3.3,3-trifluorocrotonitrile (0.45 g with a pure substance content of 85%) in dimethoxyethane. (Gas evolution was observed and a temperature rise to 30 ° ^C due to exothermic reaction). The reaction mixture is at 30 ^{° C,} cooled to room temperature, stirred for 90 min, poured into water (100 ml) and acidified to pH 16 n. hydrochloric acid. The precipitate was filtered off and dissolved in ether. The ethereal solution was dried over magnesium sulfate and concentrated in vacuo to give a brown solid. The solid was purified, turning into a slurry when mixed with a small amount of methylene chloride (10 ml), and filtered to obtain 0.39 g of the title product; so pl. 225-228 ^about S.

 PRI me R 74. Obtaining 5-bromo-2- (p-chlorophenyl) -4- (trifluoromethyl) pyrrole-3-carbonitrile.

A solution of 2- (p-chlorophenyl) -4- (trifluoromethyl) pyrrole-3-carbonitrile (0.350 g, 0.0013 mol) in dimethoxyethane was added to a solution of anhydrous sodium acetate (0.21 g, 0.0025 mol) in acetic acid , treated with a solution of bromine (0.26 g, 0.0016 mol) in acetic acid, stirred overnight at room temperature and poured into water. The resulting mixture was filtered to isolate the title product as a white solid (0.423 g) with mp. exceeding 230 ^o C.

 PRI me R 75. Obtaining ethyl 2- (3,4-dichlorophenyl) -4,4,4-trifluoroacetoacetate.

A suspension of 60% sodium hydride (7.0 g, 0.18 mol) in 200 ml of tetrahydrofuran and 200 ml of diethyl ether was treated dropwise with a solution of ethyl 4,4,4-trifluoroacetoacetate (26.8 g, 0.146 mol) in 100 ml of tetrahydrofuran was stirred at room temperature for 45 min, cooled to 5-10 and treated with a solution ^of 2-bromo-3 '4' -dihloratsetofenona (39.1 g, 0.146 mol) in 200 ml of tetrahydrofuran over a period of in 20 minutes The reaction mixture was allowed to warm to room temperature, it was heated in a vessel under reflux for five days, cooled to room temperature and slowly treated with 200 ml of water. The phases were separated, and the organic phase was washed with water (4 times 200 ml) and brine (100 ml), dried over magnesium sulfate and concentrated in vacuo to give a viscous oily liquid which solidified upon standing. The solid residue was mixed with hexanes to give the title product as a non-white solid, mp. 95-98 ^about C. This substance was directly used in the implementation of the following methods.

 PRI me R 76. Obtaining 3'4 '-dichloro-4-oxo-5,5,5-trifluorovalerophenone.

The mixture consisting of ethyl 2- (3,4-dichlorophenyl) -4,4,4-trifluoroacetoacetate (20 g, 0.054 mol) in water, acetic acid and sulfuric acid (300 ml, 300 ml, 60 ml, respectively) was heated in a reflux vessel for 15 hours, observing the evolution of carbon dioxide, cooled to room temperature and neutralized by slowly adding solid sodium bicarbonate. The reaction mixture was filtered and the filter cake was dissolved in 300 ml of ethyl acetate, dried over sodium sulfate and concentrated in vacuo to give a non-white solid. The solid was purified by vigorous stirring with cold hexanes, whereby the title product was obtained as a white solid, the amount of which was 11 g; so pl. 97-99 ^about S.

 PRI me R 77. Obtaining 2- (3,4-dichlorophenyl) -5- (trifluoromethyl) pyrrole.

A solution of 3'4 '-dichloro-4-oxo-5,5,5-trifluorovalerophenone (10.0 g, 0.033 mol) and ammonium acetate (7.7 g, 0.10 mol) in glacial acetic acid (50 ml) heated to 55-60 ^{° C,} making it as a nitrogen atmosphere, and heated for 17 hours. After cooling, the reaction mixture was poured into 300 ml of ice water, making it with rapid stirring and treated with 300 mL of dimethyl ether. The phases were separated, and the organic phase was washed several times with saturated sodium bicarbonate solution (until neutral water washings were obtained), then washed with brine, dried over sodium sulfate and concentrated in vacuo to give a dark red oily residue. Conducting evaporative chromatography of the residue on silica gel using a mixture of hexane and ethyl acetate taken in the ratio 6: 1 as the eluent, the title product (7.0 g, 75% yield) was obtained as a red oily liquid.

 PRI me R 78. Obtaining 2- (3,4-dichlorophenyl) -3-nitro-5- (trifluoromethyl) -pyrrole.

A solution of 2- (3,4-dichlorophenyl) -5- (trifluoromethyl) pyrrole (4.0 g, 0.016 mol) in acetic anhydride (30 ml) was treated dropwise at temperatures in the range from 25 to 30 ° ^C 90% fuming nitric acid (0.86 ml, 0.018 mol). The reaction mixture was stirred for 30 min at 30-40 ^{° C,} poured into 300 ml of water and stirred until the hydrolysis of acetic anhydride. The aqueous layer was decanted from a semi-solid which was taken up in ether, dried over magnesium sulfate and concentrated in vacuo to give a brown semi-solid residue, which was converted to a slurry by adding a small amount of hexane, and filtered. By chromatography (silica gel, methylene chloride), the title compound was obtained as a yellow solid with mp. 154-156 ^about S.

 Example 79. Preparation of 3-bromo-5- (3,4-dichlorophenyl) -4-nitro-2- (trifluoromethyl) pyrrole.

A solution of 2- (3,4-dichlorophenyl) -3-nitro-5- (trifluoromethyl) pyrrole (1.6 g, 0.005 mol) in dioxane was treated with a solution of bromine (0.98 g, 0.006 mol) in dioxane, stirred for nights and concentrated in vacuo to an oily residue. The residue was partitioned between ether and water. The ether layer was separated, dried over magnesium sulfate and concentrated in vacuo to an oily liquid, which gradually solidified to form a yellow solid. Recrystallization of a solid from a mixture of benzene and hexane gave the title compound as a dark yellow solid, mp. 154-156 ^about S.

 Example 80. Preparation of 2- (p-chlorophenyl) -3,5-bis (trifluoromethyl) pyrrole.

A solution of 3.0 g of 4-p-chlorophenyl-2- (trifluoromethyl) oxazolin-5-one and 2.0 g of 2-bromo-3,3,3-trifluoropropene in acetonitrile was treated with 1.2 g of triethylamine, heated at a temperature condensation under reflux for one hour and concentrated in vacuo to a residue. The residue was subjected to silica gel chromatography using a mixture of hexane and ethyl acetate taken in a ratio of 4: 1, whereby the title compound was obtained as a colorless solid in an amount of 1.6 g, mp. 41-43 ^about S.

 PRI me R 81. Obtaining 2- (p-chlorophenyl) -4-nitro-3,5-bis (trifluoromethyl) pyrrole.

A solution of 0.74 g of 2- (p-chlorophenyl) -3,5-bis (trifluoromethyl) pyrrole in acetic anhydride was treated dropwise with 0.68 ml of 90% nitric acid, stirred overnight at room temperature, heated to 35-38 ^about C and kept at this temperature for 1 h and poured into water. The mixture was extracted with ether. The ether extracts were combined, dried over magnesium sulfate and concentrated in vacuo to a residue. The residue was subjected to silica gel chromatography using a mixture of hexane and ethyl acetate taken in a ratio of 4: 1, whereby the title product was obtained as a white solid, the amount of which was 0.27 g, and so pl. was 140-143 ^about C.

 PRI me R 82. Obtaining 1- (3,4-dichlorophenyl) -4,4,4-trifluoro-1,3-butanedione.

A suspension of sodium hydride (60% suspension in mineral oil, 5.0 g, 0.125 mol) in tetrahydrofuran was heated ^to 40 ° C, treated dropwise with a solution of 3 '4' -dihloratsetofenona (15.0 g, 0.079 mol) and ethyl trifluoroacetate (11.28 g, 0.079 mol) in tetrahydrofuran, stirred for 2 hours at 40 ^{° C,} treated with isopropanol to decompose any excess quantities of sodium hydride, concentrated to half the original volume reduction and diluted with water. The mixture was extracted with a mixture of hexane with ether taken in a 1: 1 ratio. The organic extracts were combined and extracted with water. All aqueous phases were combined, acidified to pH 1 with concentrated hydrochloric acid, and extracted with ethyl acetate. The organic phase was separated, washed successively with water and a saturated solution of sodium chloride, dried over anhydrous magnesium sulfate and concentrated in vacuo to form the title product as a viscous amber oily liquid, obtained in an amount of 15.3 g.

 PRI me R 83. Obtaining ethyl-1-cyano-N- [2- (3,4-dichlorobenzoyl) -1- (trifluoromethyl) vinyl] glycinate.

A mixture of ethyl 2-cyanoglycinate (10 g, 0.078 mol) and 1- (3,4-dichlorophenyl) -4,4,4-trifluoro-1,3-butadione (18 g, 0.063 mol) in benzene was heated at a condensation temperature in a reflux condenser (using a Dean Stark trap to remove water) for 4 hours. The reaction mixture was concentrated to a brown solid, which was turned into a slurry by mixing with hexane and filtered. The filter cake was washed with cold simple ether and dried in air, obtaining the title product as a colorless solid, the amount of which was 11.8 g, etc. which was 160-164 ^about C.

 Example 84. Preparation of 3- (3,4-dichlorophenyl) -5- (trifluoromethyl) pyrrole-2-carbonitrile.

A mixture of ethyl 2-cyano-N- [2- (3,4-dichlorobenzoyl) -1- (trifluoromethyl) vinyl] glycinate (2 g, 0.005 mol) and trifluoroacetic acid (75 ml) was heated at reflux temperature in for 8 hours, poured onto ice and filtered. The white solid filter cake was dried and chromatographed on silica gel using a mixture of hexanes and ethyl acetate (taken in a 5: 1 ratio), whereby the title product was obtained as a colorless solid with mp 215-216 ^about S.

 PRI me R 85. Obtaining 4-bromo-3- (3,4-dichlorophenyl) -5- (trifluoromethyl) -pyrrole-2-carbonitrile.

A solution of 3- (3,4-dichlorophenyl) -5- (trifluoromethyl) pyrrole-2-carbonitrile (1 g, 0.003 mol) in tetrahydrofuran was treated with N-bromosuccinimide (0.76 g, 0.004 mol), stirred for 1 h and poured in a mixture of water and ethyl acetate. The organic phase was separated, washed successively with water and a saturated sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated in vacuo to a yellow solid. Recrystallization from toluene gave the title product as a white solid weighing 0.4 g with a melting point of 175-178 ^about S.

 Example 86. Preparation of 4-bromo-3- (3,4-dichlorophenyl) -2- (ethoxymethyl) -5- (trifluoromethyl) pyrrole-2-carbonyl rryl.

A solution of 4-bromo-3- (3,4-dichlorophenyl) -5- (trifluoromethyl) pyrrole-2-carbonitrile (1.0 g, 0.003 mol) in tetrahydrofuran was treated with portions of potassium tert-butoxide (0.4 g, 0.004 mol ), after which they were exposed to chloromethylethyl ether (0.4 g, 0.004 mol) in tetrahydrofuran, stirred overnight at ambient temperatures and poured into a mixture of water with ethyl acetate. The layers were separated; the organic layer was washed successively with water and a saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and evaporated to an amber semi-solid residue. The residue was converted to a slurry by mixing with hexanes, and filtered to obtain the title product as a white solid weighing 0.61 g, mp. 98-101 ^about S.

 Example 87. Following the procedure described in Example 74, but using appropriately substituted phenylpyrrol-3-carbonitrile or 3-nitro-2- (substituted) phenylpyrrole and an appropriate alkylating agent, the compounds shown below (see Tables 17 and 18).

 Example 88. By brominating the appropriate 2-aryl-5- (trifluoromethyl) pyrrole-3-carbonitrile obtained according to the procedure for Example 57 according to the procedure for Example 58, the following compounds were additionally obtained (Table 19).

 Example 89. Using the appropriate arylglycine in the procedure of Example 55 and following the procedure of Example 57, the following 2-aryl-5- (trifluoromethyl) pyrrole-3-carbonitriles were obtained (Table 20).

 PRI me R 90. Evaluation of insecticidal and acaricidal action.

All tests are prepared in advance using technical materials. All concentrations provided herein are expressed in units of active ingredient. All tests are performed at 27 ^° C

 Spodoptera eridania Southern worm at 3 stages of larval development, a semicircular lima bean leaf, extending 7-8 cm in length, immersed in the test suspension with stirring for 3 seconds and placed under a drying hood. Then the sheet is placed in a Petri dish 100x100 mm, containing wetted filter paper at the bottom and 10 caterpillars at 3 stages of development. The cup is kept 5 days before the observation of death, reduced ability to eat or any deviation from the normal state.

 Spodoptera eridania, 7 days after.

 Plants treated according to the above test are kept in the greenhouse under high-intensity lamps for 7 days. These lamps repeat the effect of a bright sunny day in June in New Jersey and incubated for a duration of 14 hours. After 7 days, foliage is collected and evaluated according to the above test.

 Aphis fabae mixed developmental stages, aphid bean. Pots containing one nasturtium plant (tropacolum sp.) About 5 cm tall infect approximately 100-200 aphids 1 day before the test. Each pot is sprayed with the test formulation with 2 sudden, violent changes in rotation at 4 rpm around the stem. For spraying use a spray De-Wilbis N 154. The tip of the spray is kept at a distance of about 15 cm from the plant and the sprayed liquid is directed in such a way as to ensure complete coverage of both plants and aphids. Pollinated pots are installed on the walls on white enameled shelves and hold for 2 days, after which the degree of killing is established.

 Tetra nychus urticae (P-resistant species), 2-spotted spider mite (see table 21).

 The semicircular lima bean plants with primary leaves, sprouted up to 7-8 cm, are selected and cut so that 1 plant is left on each pot. A small piece is cut from a sheet taken from the main colony and placed on each sheet of test plants. This is done about 2 hours before treatment to allow ticks to move around the test plant and lay their testicles. The size of the cut piece is changed so as to obtain about 100 ticks per 1 sheet. By the time of processing, the piece of leaf used to transfer the ticks is removed and discarded. Plants infected with ticks are immersed in the test formulation for 3 seconds with stirring and placed under a drying hood. Plants stand 2 days to establish dead adults, using the first sheet. The second leaf is kept on the plant for another 5 days before the next observation of the death of the testicles and / or newly hatched larvae.

 Diabrotic undecimpunctata howardi, southern root worm, 3 age stage of worm development.

1 cm ^{3 of} finely ground talcum powder is placed in a 30 ml glass jar with a wide neck and a screw cap. 1 ml of a suitable acetone suspension is pipetted onto talc so that 1.25 and 0.25 mg of the active ingredient are present in each jar. Cans are placed in a gradually moving air stream until acetone evaporates. Dried talcum powder is released and 1 cm ^{3 of} millet seeds are added to provide insect feed. Next, 25 ml of moist soil are added to each jar. The jar is closed with a lid and the contents are thoroughly mixed in a Vortex mixer. Then, 10 root worms are introduced into each jar at 3 stages of development and the jars are loosely covered with a lid to provide air exchange for the larva. Processing is continued 6 days before the counting of dead individuals begins. Missing larvae (caterpillars) were presumed dead due to their rapid decomposition, so that they could not be detected. The concentrations used for this test correspond to approximately 50 and 10 kg / ha, respectively.

Rating scale:
0 no action
1 10-20% death
2 20-35% death
3 36-45% death
4 46-55% death
5 56-65% death
6 66-75% death
7 75-85% death
8 86-99% death
9 100% killing
R reduced feed perception.

 PRI me R 91. Assessment of insecticidal action.

 Neliothis virescens 3-stage stage of development of the larva of the renal tobacco worm.

 The cotyledon of cotton is immersed in the test formulation and left to dry under a hood. After drying, each is cut into 4 parts and 10 sections, each is placed separately in 30 ml plastic medical cups 5-7 mm long pieces of moistened dental swab. One caterpillar is placed in each cup at 3 stages of age-related development and the cup is covered with cardboard loose. The treatment can withstand 3 days before proceeding to calculate the degree of death and determine the degree of reduction of feed damage.

 Empoasca abrupta, adults, Western leafy potato flea.

 The bean leaf of Sieva lima, about 5 cm long, is immersed in the test formulation for 3 s with stirring and placed under a drying hood. The sheet is placed in a Petri dish containing wet filter paper at the bottom. Approximately 10 adult leaf flea individuals are added to each dish and the treatments are held for 3 days before calculating the degree of death.

 Blatella germanica bait test, adult male German cockroach (Prussia). A 0.1% bait is prepared by pipetting 1 ml of a solution of 1000 parts per million of the test compound in acetone and applying this solution to 1 g of cornmeal, followed by adding to a 30 ml wide-necked jar. The bait is dried by carefully passing air into a jar. The bait is placed in a 0.6 L wide-necked Mason jar and 10 adult male cockroaches are introduced. The jar is closed with a mesh lid. A small piece of cotton wool, impregnated in a 10% solution of honey, is placed on top of the mesh cover laid on the jar, over the mesh cover. After 3 days, proceed to the calculation of death.

 Blatella germanica final test, adult males of a German cockroach (Prussia).

 1 ml of 1000 parts per million of the acetone solution of the test material is gradually pipetted onto the bottom of a 150x15 mm Petri dish so as to obtain a uniform coating if possible. After the applied material has dried, 10 adult male cockroaches are placed in each cup and covered with a lid. After 3 days, proceed to the calculation of death.

 Spodoptera eridania systemic exposure, stage 3 caterpillar age development. Levkanida single-point southern (mealybug).

; 10 мл ацетона и 90 мл воды. Это разбавляет 10-кратно водой, чтобы получить 100 частей на млн. эмульсию для испытания. Затем, по мере необходимости, приготовляют 10-кратные разбавления водой. Бобовые растения Sieva lima с первичными листьями длиной 7-8 см срезают на уровне по меньшей мере 3 см над поверхностью почвы. Это делают во избежание загрязнения содержащимися в почве бактериями, которые будут вызывать порчу стебля во время испытания. Срезанные стебли помещают в испытуемые эмульсии и каждый стебель оборачивают куском ваты, чтобы поддерживать стебель поверх днища банки, а также для ограничения испарения и летучести соединения. Испытание продолжают 3 дня при 27^оС для обеспечения восприятия соединений растением. После этого 1 лист удаляют от растения и помещают 100х10 мм чашку Петри с 10 левкаидами одноточечными (червецами). Испытания на степень гибели и наблюдения за повреждением корма проводят 3 и 5 днями позже.The compound is administered as an emulsion containing 0.1 g of the test material; 0.2 g of emulsifier "Emulfor El-620

; 10 ml of acetone and 90 ml of water. This dilutes 10 times with water to obtain 100 ppm emulsion for testing. Then, as needed, 10-fold dilutions with water are prepared. Legumes of Sieva lima with primary leaves 7-8 cm long are cut at least 3 cm above the soil surface. This is done to avoid contamination by bacteria in the soil that will cause stem damage during the test. Cut stems are placed in test emulsions and each stalk is wrapped with a piece of cotton wool to support the stalk over the bottom of the can, as well as to limit evaporation and volatility of the compound. The test is continued for 3 days at 27 ^{° C} to provide compounds of perception plant. After that, 1 sheet is removed from the plant and a 100x10 mm Petri dish with 10 single-point left-handed leukaids (earthworms) is placed. Tests for the degree of death and monitoring feed damage is carried out 3 and 5 days later.

 Empoasca abrupta systemic effect, adults, Western potato leaf flea.

The compound is formulated as an emulsion containing 0.1 g of the test material; 0.2 g of emulsifier "Emulfor" EI-620 ". 10 ml of acetone and 90 ml of water. This is diluted 10 times with water, which gives an emulsion of 100 ppm for testing. Then, as necessary, prepare 10-fold dilutions with water Sieva lima bean plants, whose primary leaves extend 7-8 cm, are cut at least 3 cm above the surface of the soil to prevent contamination by bacteria in the soil that will cause stem damage during the test. the stems are placed in test emulsions and each stalk is wrapped piece of cotton wool to maintain the stem over banks of the bottom and to limit evaporation and volatility of the compound. The test was continued for 3 days at 27 ^{° C} to provide the perception of plant compounds. Following this, one leaf is removed from the plant and placed in a 100x10 ml Petri dish, and carry out the determination as described above The rating scale for the above tests is the same as described in Example 90 (see Table 22).

 PRI me R 92. A) Evaluation of the tested compounds as nematicidal agents.

Culture Contents: Culture C. elegans (. Bristol strain from J. Lewis) are maintained on E.coli sections of agar plates at ²⁰ ° C. New cultures are established weekly.

 Test nematodes are washed out of cultures at 4-5 days old using fresh Ascaris Ringers (FARS). The worms are additionally washed with FARS containing gentamicin to reduce bacterial infection and centrifuged to separate the worms from the wash solution. This procedure is repeated three times. The washed worms are then added to C. briggsae medium to maintain them (CBMM) from GIBCOa, to which gentamicin (600 units / ml) and mycostatin (0.5 mg / ml) are added.

 Tests are then carried out with mixtures of three piggy backed compounds from another high-throughput screening program to reduce additional labor and connection costs.

The compounds are dissolved in acetone and adjusted to volume using equal volumes of water. For the final test, the concentration of each compound in the mixture is 150 ppm. The test material is pipetted (25 μl) into each individual cell of a sterile tissue culture plate containing 96 cells (COSTAR) ^b and the solvent is allowed to evaporate. Such “processed” plates are used immediately or stored in the freezer in the absence of obvious adverse effects on the compounds.

Freshly prepared volume (50 μg) of C. elegans in CWM is micropipeted into each treated cell and several control cells of each plate. The plates containing the culture was incubated at 20 ° ^C.

 Performance monitoring is carried out under an analytical microscope at 4, 24 and 48 hours after immersion. Immediately before the countdown, the plate is gently tapped to stimulate the movement of the worms. Activity is judged subjectively, but at the same time half quantitatively, based on the actions of the substance on the death of adult individuals and caterpillars. The criteria are as follows: 8 lack of mobility; 7 markedly reduced mobility in about 95% of worms; 6 reduced mobility; 5 slightly reduced mobility; 0 normal mobility, the same as in the control experiment. Other factors that indicate activity are easy to observe. These include paralysis, abnormal twitching, reduced reproduction in 48 hours and other deviations from normal behavior.

Test Procedure CAENORHABDITIS ELEGANS
Day 0. Inoculation of E. coli NG agar plate at 30-50 ^about C.

Incubation at 20 ° ^C.

 Day 4. Collection of a new population of C.Elegans.

 Rinsing with antibiotics.

 Transfer to SvMM.

Addition of C. Elegans (25-100 UL) to the filled cells ^a) .

Observation of activity at 4 hours after diving
Day 5. Activity Monitoring
Day 6. Activity Monitoring
Note: a) Filled cells can be prepared fresh or in advance when stored in the refrigerator.

 The data obtained during these tests are given in table. 23.

 B) Test nematodes in root nodules.

Populations of nematodes in root nodules (Meloidogyne incognita) are supported on Meteor tomatoes in a greenhouse. Testicular masses are removed from the infected root surfaces and stored on moistened filter paper for 48 hours to allow them to be excreted. Hatched larvae fall into the water near the paper. Test larvae are transferred to plate cells in the chamber containing test compounds at a concentration of 300 ppm in a 3% acetone solution in an amount of about 10 larvae. Infected cells kept at 27 ^C. The degree of killing determined 24 hours after treatment. The data obtained are given in table. 23.

 PRI me R 93. Following the above compounds according to the invention are evaluated against a number of species of insects, including: leaf flea, renal tobacco worm, single-point southern levkids and German cockroaches. The evaluation system is the same system that was used in the above examples. The data obtained are given in table. 24. In the case of two or more tests with the same test compound, one of the results is considered unnecessary. Also the symbol "-" in the table. 24 indicates no test.

 As can be seen from the data, the compounds of the invention are more effective insecticidal agents against tobacco worm larvae (Heliothis virescens) than the commercial standard agents endosulfan, acephate and sulphrophos. The tables show that the compounds of the invention are more effective acaricidal agents against two-spotted spider mites (Tetranychus urticae) than the commercial standard agents thiodicarb, amitraz and cypermethrin.

 Table test objects are defined below.

концентрация в кг/л.Test Object Scientific Name
Bean aphids aphis fabae
Legume Aphids Mixed Age
SAW / Armyworms Spodoptera eridania
Larvae of the third age stage
P.Res.Mites, Tetranychus urticae ticks
(P-resistant strain)
SCRW Diabrotic undecimpunctata howardi
3rd age stage of 11 point
Howard fleas
Leaf Hopper, Empoasa abrupta
Leaf Flea Adults Leaf Flea
western potato
TBW ³ Heliothis virscens
3rd age stage of tobacco
leaflets
G.Cockroach Blattella germania
Prussians Adult males of German cockroaches
C. Ele Caenorhabditis elegans
Nematodes of root growths Meloidogyne incognita
To recalculate the examples in kg / ha, it is necessary to proceed from the applicable volume of insecticidal, acaricidal or nematicidal spray solution. Typical volumes used for row crops are 200-500 l / ha, and for orchard crops 1250-4000 l / ha. Then, the concentration of active arrylpyrrole in the spray solution is converted from ppm to kg / l using the formula:
(concentration of arylpyrrole in ppm)

concentration in kg / l.

As soon as the concentration in kg / l becomes known, the dose in kg / ha is determined by the formula:
(concentration of arylpyrrole in kg / l) (volume of application l / ha) dose in kg / ha.

 Using the above formulas, determine the dose in kg / ha (see table. 25).

 As can be seen from the above data, the arylpyrrole compounds of the invention are effective insecticidal, acaricidal and nematicidal agents at doses of less than 4.0 kg / ha, with preferred doses being 0.125-4.0 kg / ha.

 Insecticidal Testing Protocol.

To measure the toxicity of individual insecticides at the third age stage of the tobacco leafworm (Heliothis virescens), a leaf dipping technique was used. Cotton leaves are immersed in acetone / water insecticidal solutions (50:50) and then air dried. A completely dry 2.0 x 3.0 cm portion of the treated sheet is placed in a jelly-like carrier cell containing a wet cotton dental cotton swab and an object test (third instar budworm). The cells are covered with a sheet of Mylar and sealed with a hot iron. The mortality of the larvae was evaluated 72 hours after treatment. Individual insecticidal concentrations are repeated at least 30 times. The mortality data of the larvae was subjected to probit analysis to obtain an LC ₅₀ value (lethal concentration of 50%). The results are shown in table. 26.

 Acaricidal test protocol.

Analyzes are carried out to determine the toxicity of some acaricidal compounds on two-spotted spider mites (Tetranychus urticae). Tick-infested leaves of lima beans (still connected to the plant) are immersed for three seconds in acaricidal solutions of acetone / water (50:50). Treated plants are then kept in the laboratory at a constant temperature ^of 27 C and relative humidity of 60% Percentage mite adult mortality is determined three days after treatment. Adult mite mortality data was subjected to probit analysis to obtain LC ₅₀ values (50% lethal concentration). The results are shown in table. 27.

4,5-Dichloro-2-phenylpyrrole-3-carbonitrile
4,5-Dichloro-2- (p-chloro-phenyl) -pyrrole-3-carbonitrile
4,5-Dichloro-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile
4,5-Dichloro-2- (p- (trifluoromethoxy) phenyl-pyrrole-3-carbonitrile
4,5-Dichloro-2- (o-chlorophenyl) pyrrole-3-carbonitrile
2- (p-bromophenyl) 4,5-dichloropyrrole-3-carbonitrile
4,5-Dichloro-2- (-trifluoro-p-tolyl) pyrrole-3-carbonitrile
4,5-dibromo-2- (o-chlorophenyl) pyrrole-3-carbonitrile
4,5-dibromo-2- (p-chlorophenyl) pyrrole-3-carbonitrile
4,5-Dibromo-2 (-trifluoro-p-tolyl) pyrrole-3-carbonitrile
4,5-Dichloro-2- (2,4-dichlorophenyl) pyrrole-3-carbonitrile
4,5-dibromo-2- (2,4-dichlorophenyl) -3-carbonitrile
4,5-Dichloro-2- (m-chlorophenyl) pyrrole-3-carbonitrile
2,3-Dichloro-2-nitro-5-phenylpyrrole
2,3-Dichloro-5- (p-chlorophenyl) -4-nitropyrrole
2,3-Dibromo-5- (p-chlorophenyl) -4-nitropyrrole
2,3-Dibromo-4-nitro-5-phenylpyrrole
2,3-Dichloro-5- (3,4-dichlorophenyl) -4-nitropyrrole
2- (p-bromophenyl) -4,5-dichloro-3-nitropyrrole
2,3-Dichloro-4-nitro-5- (trifluoro-p-olyl) pyrrole
Table 22
4,5-Dichloro-2-phenylpyrrole-3-carbonitrile
4,5-Dichloro-2- (p-chlorophenyl) pyrrole-3-carbonitrile
4,5-Dichloro-2- (3,4-dichlorophenyl) pyrryl-3-carbonitrile
4,5-Dichloro-2- (p-trifluoromethoxy) phenyl-pyrrole-3-carbonitrile
4,5-Dichloro-2- (o-chlorophenyl) pyrrole-3-carbonitrile
2- (p-bromophenyl) -4,5-dichloropyrrole-3-carbonitrile
4,5-Dichloro-2- (-trifluoro-p-tolyl) pyrrole-3-carbonitrile
4,5-dibromo-2- (0-chlorophenyl) pyrrole-3-carbonitrile
4,5-dibromo-2- (p-chlorophenyl) pyrrole-3-carbonitrile
4,5-Dibromo-2- (-trifluoro-p-tolyl) pyrrole-3-carbonitrile
4,5-Dichloro-2- (2,4-dichlorophenyl) pyrrole-3-carbonitrile
4,5-dibromo-2- (2,4-dichlorophenyl) pyrrole-3-carbonitrile
4,5-Dichloro-2- (m-chlorophenyl) pyrrole-3-carbonitrile
2,3-dichloro-4-nitro-5-phenyl-pyrrole
2,3-Dichloro-5- (p-chlorophenyl) -4-nitropillol
2,3-Dibromo-5- (p-chlorophenyl) -4-nitropyrrole
2,3-Dibromo-4-nitro-5-phenyl-pyrrole
2,3-Dichloro-5- (3,4-dichlorophenyl) -4-nitropyrrole
2- (p-bromophenyl) -4,5-dichloro-3-nitropyrrole
2,3-Dichloro-4-nitro-5- trifluoro-p-tolyl) pyrrole.

Table 23
4,5-Dichloro-2- (p- (trifluoromethoxy) phenyl-pyrrole-3-carbonitrile
4,5-Dichloro-2- (-trifluoro-p-tolyl) pyrrole-3-carbonitrile
4,5-Dibromo-2- (-trifluoro-p-tolyl) pyrrole-3-carbonitrile
2,3-Dichloro-4-nitro-5-phenylpyrrole
2,3-Dichloro-4-nitro-5-phenylpyrrole
2,3-Dichloro-5- (p-chlorophenyl) -4-nitropyrrole
2,3-Dichloro-5- (3,4-dichlorophenyl) -4-nitropyrrole
2- (p-bromophenyl) -4,5-dichloro-3-nitropyrrole
2,3-Dichloro-4-nitro-5- (trifluoro-p-tolyl) pyrrole
Table 24
2,5-Dichloro-4-phenylpyrrole-3-carbonyryl
2,3-Dibromo-4-nitro-5-phenyl-pyrrole
4-chloro-2- (p-chlorophenyl) pyrrole-3-carbonitrile
4,5-Dichloro-2- (0-chlorophenyl) pyrrole-3-carbonitrile
5-Bromo-2- (p-chlorophenyl) pyrrole-3-kaarbonitrile 4,5-Dichloro-2- (3,4-dichlorophenyl) -1- (ethoxymethyl) pyrrole-3-carbonitrile
4,5-Dichloro-2- (p-chlorophenyl) -1-methyl-pyrrole-3-carbonitrile
p- (4,5-dichloro-3-cyanopyrrol-2-yl methylene benzoate
4,5-dibromo-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile
4,5-Dichloro-2- (-trifluoro-m-tolyl) -pyrrole-3-carbonitrile
4,5-Dichloro-2- (3,4-dichlorophenyl) -1-ethyl-pyrrole-3-carbonitrile
4,5-Dichloro-2- (3,4-difluorophenyl) pyrrole-3-carbonitrile
4,5-Dichloro-2- (3,4-dichlorophenyl) -1-methylpyrrole-3-carbonitrile
4,5-Dichloro-2- (p- (methylsulfonyl) phenyl) pyrrole-3-carbonitrile
4,5-Dibromo-1-methyl-2- (trifluoro-p-tolyl) pyrrole-3-carbonitrile
4,5-Dichloro-2- (p-fluorophenyl) pyrrole-3-carbonitrile
4,5-Dibromo-2- (3,4-difluorophenyl) pyrrole-3-carbonitrile
4,5-Dibromo-2- (p-fluorophenyl) pyrrole-3-carbonitrile
4,5-Dibromo-2- (p-nitrophenyl) pyrrole-3-carbonitrile
4,5-Dichloro-2- (p-nitrophenyl) pyrrole-3-carbonitrile
1-Benzyl-4,5-dibromo-2- (alpha-alpha, alpha-trifluoro-p-tolyl) pyrrole-3-carbonitrile
4,5-Dichloro-2- (p-dianophenyl) pyrrole-3-carbonitrile
4,5-Dibromo-2- (p- (methylsulfonyl) phenyl) pyrrole-3-carbonitrile
4,5-Dibromo-2- (p-chlorophenyl pyrrole-3-carbonitrile 4,5-Dichloro-2- (3,4-dichlorophenyl) -1- (2- (methylthio) ethyl) pyrrole-3-carbonitrile
1-Methyl-4,5-dichloro-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile
4,5-Dichloro-1-methyl-2- (alpha, alpha-alpha-t rifluoro-p-tolyl) pyrrole-3-carbonitrile
5-bromo-4-chloro-2- (p-chlorophenyl) pyrrole-3-carbonitrile
2,3-Dichloro-5- (3,4-dichlorophenyl) -1-ethoxymethyl) -4-nitropyrrole
4-bromo-5-chloro-2- (p-chlorophenyl) pyrrole-3-carbonitrile
1-Benzyl-4,5-dichloro-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile
Ethyl 2,3-dichloro-5- (3,4-dichlorophenyl) -4-cyanopyrrole-1-acetate
4,5-Dichloro-1- (ethoxymethyl) -2- (alpha, alpha, alpha-trifluoro-p-tolyl) pyrrole-3-carbonitrile
3-Bromo-5- (3,4-dichlorophenyl) pyrrole-2,4-dicarbonitrile 4,5-Dichloro-2- (3,4-dichlorophenyl) -1-1- (2-propynyl) pyrrole-3-carbonitrile
4,5-dibromo-3- (p-chlorophenyl) pyrrole-2-carbonitrile
5- (3,4-Dichlorophenyl) pyrrole-2,4-dicarbonitrile
5-bromo-4-chloro- (3,4-dichlorophenyl) pyrrole-3-carbonitrile
4,5-Dibromo-3- (p-chlorophenyl) -1-methylpyrrole-2-carbonitrile
2-bromo-5-phenyl-pyrrole-3,4-dicarbonitrile
4-bromo-2-phenyl-5- (trifluoromethyl) pyrrole-3-carbonitrile
2- (3,4-Dichlorophenyl) -5-nitropyrrole-3-carbonitrile
4-bromo- 2- (3,4-dichlorophenyl) -5-nitropyrrole-3-carbonitrile
2,4-Dibromo-5-phenylpyrrole-3-carbonitrile
2- (3,4-dichlorophenyl) -4,5-diiodopyrol-3-carbonitrile
2,3-Dibromo-5- (p-chlorophenyl) -1-ethoxymethyl-4-nitropyrrole
1-Benzyl-2,3-dibromo-5- (p-chlorophenyl) -4-nitropyrrole
2,3-Dibromo-5- (p-chlorophenyl) 1-methyl-4-nitropyrrole
4,5-Dibromo-2- (p- (trifluoromethoxy) phenyl) pyrrole 3-carbonitrile 4,5-Dichloro-1- (ethoxymethyl) -2- (p- (trifluoromethoxy) phenyl) pyrrole-3-carbonitrile
5- (P-chlorophenyl) pyrrole-2,4-dicarbonitrile
1-Benzyl-4,5-dichloro-2 (p- (trifluoromethoxy) phenyl) pyrrole-3-carbonitrile
4,5-Dichloro-2- (p-chlorophenyl) -1- (ethoxymethyl) pyrrole-3-carbonitrile
4,5-Dichloro-2- (3,4-dichlorophenyl) -1- (2-hydroxyethyl) pyrrole-3-carbonitrile
2- (P-chlorophenyl) -5-nitropyrrole-3-carbonitrile
4-bromo-2- (p-chlorophenyl) -5-trifluoromethyl) pyrrole-3-carbonitrile
4-bromo-2- (p-chlorophenyl) -5-nitropyrrole-3-carbonitrile
3-bromo-5- (p-chlorophenyl) pyrrole-2,4-dicarbonitrile
4,5-Dichloro-2- (3,4-dichlorophenyl) pyrrole-1,3-dicarbonitrile 1 - ((Benzyloxy) methyl) -4,5-dichloro-2- (3,4-dichlorophenyl) pyrrole-3- carbonitrile
4,5-Dichloro-2- (2,4-dichloro-5-fluoro-phenyl) pyrrole-3-carbonitrile
5- (P- (trifluoro-methoxy) phenyl) pyrrole-2,4-dicarbonitrile 4,5-Dichloro-1 - ((p-chlorophenoxy) methyl-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile
4,5-Dichloro-2- (3,4-dichlorophenyl) -1- (3-iodo-2-propinol) pyrrole-3-carbonitrile
5- (3,4-Dichlorophenyl) -4-nitro-pyrrole-2-carbonitrile
2,4-Dibromo-5- (p-chlorophenyl) pyrrole-3-carbonitrile
3-bromo-5- (p- (trifluoromethoxy) phenyl) pyrrole-2,4-dicarbonitrile
3-Bromo-5- (3,4-dichlorophenyl) 4-nitropyrrole) -2-carbonitrile 4-Bromo-2- (p-chlorophenyl) -1-methyl-5- (trifluoromethyl) pyrrole-3-carbonitrile
3,4-Dibromo-5- (3,4-dichlorophenyl) pyrrole-2-carbonitrile
2- (3,4-Dichlorophenyl) -5-trifluoromethyl) pyrrole-3-carbonitrile
5- (trifluoromethyl) -2- (alpha, alpha, alpha-trifluoro-p-tolyl) pyrrole-3-carbonitrile
2,5-Dibromo-4- (p-chlorophenyl) pyrrole-3-carbonitrile
3,5-dibromo-4- (p-chlorophenyl) pyrrole-2-carbonitrile
2-P-tolyl-5- (trifluoromethyl) pyrrole-3-carbonitrile
4-Bromo-2-p-tolyl-5- (trifluoromethyl) pyrrole-3-carbonitrile 4-Bromo-2- (p-chlorophenyl) -1- (ethoxymethyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile
4-bromo-2- (3,4-dichlorophenyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile
5 (alpha, alpha, alpha-trifluoro-p-tolyl) pyrrole-2,4-di carbonitrile
1-Methyl-3- (alpha, alpha, alpha-trifluoro-p-tolyl) pyrrole-2,4-dicarbonitrile
4-Bromo-5- (trifluoromethyl-2- (alpha, alpha, alpha-trifluoro-p-tolyl) pyrrole-3-carbonitrile
3-Bromo-1-methyl-5- (alpha, alpha, alpha-trifluoro-p-tolyl) pyrrole-2,4-dicarbonitrile
4,5-Dichloro-2- (alpha, alpha, alpha-trifluoro-p-tolyl) pyrrole-1,3-dicarbonitrile
3-Bromo- (alpha, alpha-alpha-trifluoro-p-tolyl) pyrrole-2,4-dicarbonitrile
Table 25
Table 26
Table 27

Claims (4)

1. Derivatives of arylpyrrole of the general formula

where X is chlorine, bromine, iodine or CF ₃ ;
Y is chloro, bromo, iodo, CF ₃ or CN;
W CN or NO ₂ ;
And hydrogen, C ₁ -C ₄ alkyl unsubstituted or substituted by halogen, hydroxy, C ₁ -C ₄ alkoxy, C ₁ -C ₄ alkylthio or phenyl group, phenoxy or C ₁ -C ₂ alkoxyphenyl group , C ₁ -C ₄ -carbalkoxymethyl, C ₃ -C ₄ alkenyl unsubstituted or substituted with one halogen, cyano, C ₃ -C ₄ alkynyl unsubstituted or substituted with one halogen, di (C ₁ -C ₄ ) alkylaminocarbonyl,
L is hydrogen, fluoro, chloro or bromo;
M and R are each independently hydrogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ alkoxy, C ₀ -C ₃ alkylsulfonyl groups, cyano, fluoro, chloro, bromo, iodo, nitro, CF ₃ , groups R ₁ CF ₂ Z or R ₂ CO, where Z is oxygen, R _{1 is} fluorine or CHF ₂ , R ₂ is C ₁ C ₃ -alkyl, and when the groups M and R are in adjacent positions, they, together with the carbon atoms to which they are attached, form a ring where the MR group is —CH═CH — CH═CH—. 2. A method of producing derivatives of arylpyrrole of the general formula according to claim 1, characterized in that benzoylacetonitrile or α-nitroacetophenone of the general formula

where L, M, R and W have the meanings indicated in paragraph 1, are reacted with 2,2-di (C ₁ C ₄ -alkoxy) ethylamine, the resulting α - [2,2-di (C ₁ - C ₄ -alkoxy) ethylamino] -b-cyanostyrene or a - [2,2-di (C ₁
C ₄ -alkoxy) ethylamino] b nitrostyrene is treated with a mineral or organic acid. 3. a [2,2-Di (C ₁ -C ₄ -alkoxy) ethylamino] -b-cyanostyrene or a - [2,2-Di (C ₁ -C ₄ -alkoxy) ethylamino] b-nitrostyrene of the general formula;

where L, M, R and W have the indicated meanings.  4. A method for controlling insects, nematodes and ticks by treating them with an arylpyrrole derivative, characterized in that the compound of general formula I (where the radical values are given in paragraph 1) is used as arylpyrrole in effective quality.

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